Tag Archives: mitochondrial damage

Floxie Hope Email List and Free Ebook



After 2.5 years, and more than 200 posts, I’m finally starting an email list for Floxie Hope. 🙂

If you sign up for the email list, you will get healing tips, links to interesting studies, updates on the recovery progress of those who have recovery stories on Floxie Hope, and more. You can sign up for the email list through this link – http://forms.aweber.com/form/15/753869915.htm – or through clicking the picture above.

You will also get a FREE EBOOK called HACKING FLUOROQUINOLONES if you sign up for the email list.

Hacking Fluoroquinolones describes the multiple levels of damage that fluoroquinolones do. Fluoroquinolones damage mitochondria, they leach minerals out of cells, they damage the microbiome, they damage the thyroid, and more. Information about each of these damage mechanisms is noted in Hacking Fluoroquinolones.

Thank you to all who sign up for the email list! I promise to share good information with you!

I won’t send you spam or share your email address with anyone else. As is the case with all legal email lists, you can unsubscribe at any time.

Many people already “follow” Floxie Hope. Thank you to all who do! This email list is different from “following” this site. When you follow Floxie Hope, you are sent an email whenever a post goes up. If you subscribe to the email list, you will receive the Hacking Fluoroquinolones ebook and follow-up emails with useful tips and information. You are welcome (and encouraged) to do both.

Thank you all for your support! I hope that Hacking Fluoroquinolones, and all the information on Floxie Hope, is helpful to you!



Change the Warning Labels: Why it Matters

The warning label for Cipro/ciprofloxacin is already 43 pages long. It includes warnings about devastating adverse effects including irreversible peripheral neuropathy, destruction of weight-bearing joints, prolongation of the QT interval, seizures, severe hepatotoxicity, Stevens-Johnson syndrome, “psychotic reactions (that) have progressed to suicidal ideations/thoughts and self-injurious behavior such as attempted or completed suicide,” and more. Most of the symptoms of fluoroquinolone toxicity are already listed on the warning label. But when patients go to their doctors with symptoms of fluoroquinolone toxicity, they are often told that their reaction couldn’t be from the Cipro, Levaquin, Floxin or Avelox they took. To say that it’s frustrating that many doctors aren’t aware of the side-effects that ARE LISTED ON THE WARNING LABELS, is an understatement. It is shameful that the adverse effects listed on the warning labels aren’t known and quickly acknowledged by all medical professionals. It’s bad enough that many of those practicing medicine don’t know how to help people heal from fluoroquinolone toxicity, the fact that the symptoms that are listed on the warning labels aren’t often acknowledged, is horrible.

What’s the Point of the Warning Label?

It begs the question, if adverse-effects that are listed on the warning label aren’t being acknowledged, what is the point of the warning label?

One could argue that the only purpose of the warning label is to protect the pharmaceutical companies from being sued. After all, if you are hurt by a drug in a way that is listed on the warning label, most lawyers won’t take your case, and suing the drug companies for damage done is difficult to impossible.

Since patients are rarely given complete warning labels with their prescriptions for fluoroquinolones, and because the lengthy warning labels are still inadequate, and because the Learned Intermediary Doctrine makes it so that there are no requirements that patients even be informed about the consequences of taking prescription drugs, one could certainly argue that drug warning labels don’t protect consumers at all.

Citizen’s Petitions for Changing Fluoroquinolone Warning Labels

There are two citizen’s petitions that have been filed with the FDA asking for additional warnings to be added to the warning labels for Levaquin/levofloxacin (that would likely carry over to the other fluoroquinolones too). One of the petitions is for adding additional warnings of psychiatric adverse events, and the other is for adding “Possible Mitochondrial Toxicity” to the warning labels.

Since the existing warning labels are so inadequate for actually warning doctors or patients, and are actually counterproductive for patients seeking justice for the harm done to them, many people have asked, “What’s the point in adding anything to the warning label?” and they have asserted that adding more warnings to the labels isn’t what we should be aiming for.

In many ways, I agree with their assertions. If warning labels aren’t adequate or heeded, and if they actually get in the way of justice, we should be fighting for something other than more additions to the warning labels. We should be fighting for severe restrictions of these drugs, as well as true informed consent where all possible adverse effects are gone over with patients prior to administration of fluoroquinolones, similar to the restrictions put on Warfarin and Coumadin. We should fight for awareness of fluoroquinolone toxicity, so that doctors know about the possible harm they can do to patients with these drugs, so they can avoid doing that harm. We should fight for more research into fluoroquinolones so that the damage done by them can be more fully understood. We should fight for cures and assistance for those who have been hurt by fluoroquinolones. We should fight for justice, and more.

Many people and organizations ARE fighting for these things. Media outreach efforts are raising awareness and the doctors who are reached by these media reports are using fluoroquinolones more prudently. For example, it was reported that prescriptions for Levaquin/Levofloxacin dropped significantly after “Local woman says popular antibiotic killed her husband” aired and was shared more than 135k times on social media. The Quinolone Vigilance Foundation (QVF) works with scientists researching fluoroquinolones. Many people have written letters to their Representatives, the FDA and the AMA asking that stronger restrictions be put on fluoroquinolones. Several law firms are suing Bayer and Johnson & Johnson on behalf of fluoroquinolone victims. These things are all moves in the right direction.

Throwing a Punch at the Drug Companies

Receiving a positive response from the FDA to the Citizens’ Petitions is also a move in the right direction. Adding psychiatric adverse events and mitochondrial toxicity to the warning labels is actually a huge weapon for floxie advocates. Warning labels themselves may be useless, but during the time when a warning label has things added to it, they can be a great tool, and a big gun we can use against the pharmaceutical companies. The ONLY times lawyers are willing to take cases to sue the drug companies are when warning labels change. For example, when the fluoroquinolone warning labels were adjusted in August, 2013 to note that permanent peripheral neuropathy is a possible effect of fluoroquinolones, several law firms took cases of those who are suffering from peripheral neuropathy after taking fluoroquinolones. Before the warning label changed, they wouldn’t take the cases, because, appallingly, you can’t sue drug companies for hurting you, you can only sue them for “failure to warn” of the harm they’ll do. It’s a really stupid situation and stupid system. BUT, the time when warning labels change is the brief period of time in which you can sue the drug companies for “failure to warn” and it’s the brief period of time when we have the chance to fight the pharmaceutical companies. Opening this window is a good thing, and I support the Citizen’s Petitions because they are wonderful “window openers.” I hope that the FDA responds positively to them, and adds both psychiatric adverse events and “Possible Mitochondrial Toxicity” to the warning labels for all fluoroquinolones.


If the window for justice can be opened by the Citizen’s Petitions, we may be able to throw a big punch that actually hurts Bayer and/or J&J. If psychiatric adverse events are added to the warning labels, ANYONE who has suffered from a psychiatric illness who had previously taken Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin or Floxin/ofloxacin can sue the drug companies that produce fluoroquinolones. That’s a lot of people who can, potentially, take a chunk of change out of Bayer’s and J&J’s pockets.

Mitochondrial toxicity is linked to many diseases, including all autoimmune diseases, neurodegenerative diseases, fibromyalgia, autism, CFS/ME, cancer, psychiatric illness, obesity, etc. Adding mitochondrial toxicity to fluoroquinolone warning labels opens the possibility for a HUGE punch to the pharmaceutical companies. If it is fully acknowledged that fluoroquinolones cause mitochondrial toxicity, anyone who comes down with a disease that is linked to mitochondrial toxicity can sue the manufacturer of the drug that hurt them. If everyone who got sick with a chronic disease who had previously taken a fluoroquinolone was able to sue Bayer or J&J, the drug companies would take note, and change may even occur.

It will be difficult for the FDA to claim that “possible mitochondrial toxicity” shouldn’t be added to fluoroquinolone warning labels. After all, it is stated IN THEIR DOCUMENT entitled, “Disabling Peripheral Neuropathy Associated with Systemic Fluoroquinolone Exposure,” that:

Ciprofloxacin has been found to affect mammalian topoisomerase II, especially in mitochondria. In vitro studies in drug-treated mammalian cells found that nalidixic acid and ciprofloxacin cause a loss of motichondrial DNA (mtDNA), resulting in a decrease of mitochondrial respiration and an arrest in cell growth. Further analysis found protein-linked double-stranded DNA breaks in the mtDNA from ciprofloxacin-treated cells, suggesting that ciprofloxacin was targeting topoisomerase II activity in the mitochondria.”

THEY acknowledge that fluoroquinolones deleteriously affect mitochondrial DNA. The least they could do is put that information on the warning labels.

Movement…. Hopefully in the Right Direction

I obviously have a lot of conflicting feelings about changing the fluoroquinolone warning labels. I wish that we, as citizens who have been hurt by these drugs, had more opportunities for enacting change. I also wish that the warning labels were meaningful documents that were heeded by doctors and patients alike, and that they didn’t primarily serve the pharmaceutical companies. I also wish that more victims of fluoroquinolones were able to gain justice BECAUSE THEY WERE WRONGLY HURT BY A PRESCRIPTION DRUG, rather than making them jump through legal loop-holes about “failure to warn.” Until those things change though, we need to use the tools and opportunities we have. If enacted, the Citizen’s Petitions give us an opportunity to throw a big punch.

I hope that the FDA changes the warning labels to reflect what is known about fluoroquinolones causing mitochondrial toxicity and psychiatric adverse events.  If the warning labels change, and the punch behind the mitochondrial toxicity and psychiatric adverse events is big enough, maybe real change will occur. We can hope.


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Petitioning the FDA – Comments Needed

Floxie friends, I have one thing that I am asking you to do today.  And please, if you decide to do it, do it sooner rather than later.  Please go to THIS LINK and make a comment about how fluoroquinolones have hurt you.  Let the FDA know that the current warning label for fluoroquinolones is insufficient.  Let the FDA know that their own findings of fluoroquinolone caused mitochondrial toxicity need to be noted on the warning labels of fluoroquinolones.

Again, here is the link for the citizens’ petition, filed with the FDA, where comments about how a fluoroquinolone hurt you can be made –


If you do nothing else today, please, please make comments on this petition.

Thank you!

HERE is the petition that I am asking you to comment on.

The petition was submitted by Dr. Charles Bennett, M.D., Ph.D., M.P.P.  Dr. Bennett is with the Center for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR).  The Quinolone Vigilance Foundation facilitated much of the work that went into the petition.  I thank both Dr. Bennett and his colleagues, and the Quinolone Vigilance Foundation for their work!

The petition is to add “Possible Mitochondrial Toxicity” to the Levaquin label.  In the Warnings and Precautions section of the Levaquin/levofloxacin label, it should say:

Possible Mitochondrial Toxicity

Fluoroquinolones, including Levaquin, may cause Mitochondrial Toxicity due, in part, to an insufficiency of ATP. Mitochondrial conditions that are due to an insufficiency of ATP include developmental disorders of the brain, optic neuropathy, neuropathic pain, hearing loss, muscle weakness, cardiomyopathy, and lactic acidosis. Neurodegenerative diseases, like Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) have been associated with the loss of neurons due to oxidative stress generated by reactive oxygen species (ROS) related to Mitochondrial Toxicity. Peripheral neuropathy, hepatoxicity, glucose disturbances, and phototoxicity may result from Mitochondrial Toxicity.

That language, by the way, is directly from the FDA document, “Disabling Peripheral Neuropathy Associated with Systemic Fluoroquinolone Exposure.”  The folks at the FDA know that fluoroquinolones have been shown to be toxic to mitochondria, this petition is asking them to do something about it.

It is also requested in the petition that the following black box warning be added to the Levaquin/levofloxacin warning label:


Fluoroquinolones may cause Mitochondrial Toxicity. Mitochondrial Toxicity has been implicated in conditions such as peripheral neuropathy, hepatoxicity, glucose disturbances, phototoxicity, developmental disorders of the brain, optic neuropathy, neuropathic pain, hearing loss, muscle weakness, cardiomyopathy, lactic acidosis, Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS).

Based on the severity of the effects of mitochondrial toxicity, it is being requested that:

  1. Levaquin label changes be made immediately.
  2. “Dear Doctor” letters be distributed regarding Levaquin label changes and requesting that physicians inform patients about the potential impact of “Possible Mitochondrial Toxicity” if they were previously prescribed this drug.

It is very important for all patients and medical professionals that this warning be added to the label of fluoroquinolones.  Please make your voice heard and support the petition with your comments.



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Dr. Robert Rountree’s Presentation about Mitochondria

I highly recommend that you watch this –


It’s a video of Dr. Robert Rountree giving a presentation about mitochondria. It’s fascinating!

Fluoroquinolones damage mitochondria. Here are my posts about fluoroquinolones damaging mitochondria –

There are more interesting posts about mitochondria on Hormones Matter, and probably some other sites too.

I try to make this complex information a bit more comprehensible than it is in journal article format, but if you want to read through some source articles on how fluoroquinolones damage mitochondria, here are some good ones:

Also, at roughly minute 26 of Dr. Rountree’s presentation, he mentions the link between cardiolipin damage and autoimmune diseases. Here is an article about how fluoroquinolones affect cardiolipin –

Journal of Medical Microbiology, “Comparison of the Effects of Subinhibitory Concentrations of Ciprofloxacin and Colistin on the Morphology of Cardiolipin Domains in Escherichia Coli Membranes

Dr. Rountree is brilliant and I don’t mean to be critical, but I think that some of the graphs toward the end of the presentation need to be re-drawn. From what I understand from reading the above articles, and others on mitochondria, the effects of ROS (reactive oxygen species – also known as oxidative stress), are not linear. When mitochondria experience a healthy amount of stress – through exercise, for example – there is an adaptive response. It is actually likely that the initial response of mitochondria to fluoroquinolones is an adaptive and healthy one – that could explain some of the experimental results that show a healthy or adaptive response of cells to fluoroquinolones. It is only after the threshold for damage is crossed that a maladaptive/unhealthy response begins. And once that maladaptive/unhealthy response begins, well, it’s bad news because the cell perpetuates damage on itself in the “vicious cycle” of mitochondrial damage. This article explains the phenomenon of a threshold for mitochondrial damage well –

Molecular Interventions, “Mechanisms of Pathogenesis in Drug Hepatoxicity Putting the Stress on Mitochondria

Can the cycle of cellular damage be stopped? I think so. If feeling good is an indicator of health, I know so. As always, I hope the same for all of you!

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Fluoroquinolone Antibiotics Damage Mitochondria – FDA Does Little

Hormones Matter Logo2

The Pharmacovigilance folks at the FDA know that fluoroquinolones are damaging mitochondria.  Yet, they look the other way.  Adding a more severe warning about peripheral neuropathy to the warning label isn’t helpful.  People should know that they are increasing their risk of every chronic disease associated with mitochondrial damage and oxidative stress when they take a fluoroquinolone.  That would actually be helpful.

Here is the post, on Hormones Matter – http://www.hormonesmatter.com/fluoroquinolone-antibiotics-damage-mitochondria-fda-adds-warning/


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Can Antibiotics Induce Psychiatric Reactions?

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Fluoroquinolones cause mitochondrial damage and oxidative stress.  Mitochondrial damage and oxidative stress have been causally linked to all sorts of psychiatric disorders, including, but not limited to bipolar disorder, depression, attention deficit hyperactivity disorder, anxiety, etc.  Fluoroquinolones are bad for your brain.  Reactive oxygen species have hugely deleterious effects on all parts of the body and mind.


The full post can be found here –



Thank you, as always, for reading and sharing information about the dangers of fluoroquinolones!


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The Fluoroquinolone Time-Bomb – answers in the Mitochondria

Adverse reactions to fluoroquinolones are often delayed and people can tolerate a certain number of fluoroquinolones before they experience an adverse reaction. Delayed reactions and tolerance thresholds are perplexing mysteries until you take a look at mitochondrial dysfunction. Both delayed reactions and tolerance thresholds are actually typical for disease states that are caused by mitochondrial dysfunction. More details on the matter in this post. As always, thank you for reading and sharing!



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Have you seen the documentary, “I AM?”  It’s an interesting and insightful film.  I recommend it.  Here it is, for you to check out:

The film makers seek to find answers to two questions.

1.  What is wrong with our world?


2.  What are the solutions to the world’s problems?

(Spoiler alert) – The answer to both questions is the same.  It is –


I am what is wrong with the world.  I am the solution to the world’s problems.

Kinda profound, if I do say so myself.

We all have problems and solutions within us.  I assert that they are in balance as well.  Those who cause huge problems are a huge part of the solutions.  Those who cause small problems are still part of the solutions, but they’re a smaller part.  People fluctuate between perpetuating problems and perpetuating solutions.  The pendulum swings from problem to solution – in our individual lives, in our institutions and in our world.

No one is the solution without recognizing that they are the problem as well.  There are those who are the problem without being the solution, but they generally fail to recognize that they are part of the problem – they fail to see that there is a problem and imagine, out of ego and narcissism, that they are neutral.

It’s called responsibility.  I am responsible for the problems that I cause in the world and I am responsible for solutions to them.

It took a long time for me to accept responsibility for my floxing, and I sill like to think of myself as more of a contributor to the solution than to the problem of people being hurt by fluoroquinolones.  Sure, I can take responsibility for putting the pills in my mouth, for self-medicating, for having a breakdown when I got sick, for not communicating what happened to me to my doctor, for the anger that I feel toward the medical system, and plenty more.  Got it.  I am responsible for all of those things.  I am also responsible for creating this site to bring light to the problem, for offering people stories of hope and healing, along with snippets of “deep thoughts by Lisa” – these things are part of the solution.  They’re the least that I can do and I have every intention of doing more to change the situation of people becoming disabled from unnecessarily strong chemotherapy drugs being frivolously prescribed to treat infections.  My pendulum is in solution mode for the problem of fluoroquinolone toxicity.  And fluoroquinolone toxicity is a problem, a big one.

Doctors, and the medical system as a whole, don’t seem to see the problem though.  They are stuck in the narcissistic, false view that they are the solution without being part of the problem.  They fix things, cure diseases and heal people, right?  Sure – those things happen.  Doctors should be proud of every life that they save and every disease that they cure.  But those accomplishments do not diminish the pain that they inflict.  Along with the good that has come with modern medicine, harm has come as well.  The rise in “diseases of modernity” such as autoimmune diseases, obesity and its complications, ignored diseases (like fibromyalgia, chronic fatigue, gulf war syndrome, adverse drug reactions, etc.), autism, mental illness (it’s not a choice), dietary intolerances, etc. are at least partially, if not fully, caused by pharmaceuticals, doctors and the medical system.

It’s not that difficult of a concept – pharmaceuticals cause mitochondrial damage, those mitochondria create massive amounts of oxidative stress and the superoxide and/or peroxynitrate cycles within the cells cause direct and indirect (through damage to DNA and negative gene expression) harm.  Also, destruction of the microbiome and its balance are really bad ideas that cause all sorts of problems.

Of course, the whole process is complex and difficult to understand when you get into the details.  It’s too difficult for most doctors to see, not only because it’s hard and they’re too busy to look at scientific research, but also because they’re stuck in their ideas of what “should” be.  Drugs “should” metabolize out of a person’s body in a short amount of time.  Antibiotics “should” kill bacterial cells while leaving host cells intact.  Fluoroquinolones “should” not damage DNA.  Doctors “should” cure diseases.  The medical system “should” be the solution, not the problem.

Too bad what “should” be does not align with what IS.

Every doctor, every drug, even every patient that buys into the system, is part of the problem.

It is time for everyone to recognize that with the good of Western medicine, some bad has come too.  It’s time for egos to be put aside and for people (mainly the doctors) to realize that they are responsible for recognition and creation of the problem – they are the problem.

Doctors and other people in the medical system are the solution as well.  Of course they are!  Who else could be?  They have the resources to solve the problems that they cause, and no one else does.

Patients are part of both the problem and the solution as well.  The information is available for patients to realize a large amount of what good and harm drugs and procedures do.  Patients can, and should, advocate for themselves and speak out when they see something that is wrong.

But first, both doctors and patients have to see that there are problems.  They need to see that the situation that we are in, with young people falling ill to chronic, disabling diseases, is not okay.  It’s a problem.

I can only hope that doctors will be willing to put aside their foolish egos and realize that they do harm along with good.  They aren’t going to realize anything or accept any culpability without pressure.  I am sure of that.  People who have been hurt by them (and the system that they are part of) need to rise up and make them aware of the harm that they have caused; the problems that their actions have led to.

Patient activists are responsible for putting pressure on doctors, the pharmaceutical companies, pharmacists, and others in the medical field too.  We need to push harder so that those within the system are recognizing the problem and working toward becoming the solution.

I AM the solution.  (Along with cannabis – haven’t you heard?  It cures EVERYTHING.)

I AM the problem as well.  (Along with fluoroquinolones – seriously, I can connect them causally to every chronic illness out there.)

I have less power than the medical system and the pharmaceutical industry though, so, dare I say – I am less of the problem, or the solution than they are.

Solution mode is greatly needed.  From everyone.  Especially from those with power and influence.

Maybe my perceived lack of power is a cop-out though.  Maybe the answer is simple.  What is the problem?  I AM.  What is the solution?  I AM.

You are too.

“No man sets aside his old ways to seek the new until he personally feels the need for it.  This is why the great teachers urge men to see the awful condition they are actually in, rather than living by pretty words and nonexistent ideals.  Talking about love and peace when neither love nor peace are in their hearts is a cunning and destructive evasion of the facts.”  – Vernon Howard


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Article Breakdown – “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria”

Do you have a headache?  Do you want one?  If so, read this article –

Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria” written by

Dean P. Jones, John J. Lemasters, Derick Han, Urs A. Boelsterli, Neil Kaplowitz

If you want a headache that lasts a while, read these articles that give background information as to why what is in “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria” is important.

Drug Metabolism and Disposition, “Acyl Glucuronidation of Fluoroquinolone Antibiotics by the UDP-Gulucuronosyltransferase 1A Subfamily in Human Liver Microsomes


Current Drug Metabolism, “Acyl Glucuronides: Mechanistic Role in Drug Toxicity?

Despite their headache inducing capabilities, the articles are actually quite interesting and important.  To highlight how and why they are important, here is my breakdown of “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria.”  As I have done with other journal articles, I have taken quotes from the article and commented under them.

“Mitochondrial impairment is usually a final event common to pathways leading to necrotic and apoptotic cell death.”

Since mitochondrial impairment leads to cell death, perhaps it would be nice for the FDA to examine how pharmaceuticals affect mitochondria before approving them.  Sadly, they don’t think so, as “mitochondrial toxicity testing is still not required by the US FDA for drug approval.” (http://psychrights.org/Research/Digest/NLPs/DrugsCauseMitochondrialDamage.pdf)

“it is important to consider whether drug-induced participation of mitochondria in hepatocellular death is a direct result of drugs acting on these organelles (e.g., drug accumulation, inhibition of electron transport and fatty acid oxidation, or depletion of anti-oxidant defense) or an indirect result ensuing from mitochondrial participation in programs of cell death.”

They found that both were the case.  This stuff is very complex and not linear.  One reaction causes another reaction, on and on for a while.  It’s not an either/or situation.

“Oxidative stress is often defined as an imbalance of pro-oxidants and antioxidants; however, the finding that thiols [i.e., glutathione (GSH) and cysteine (Cys)] in plasma are not in redox equilibrium with their disulfide products [i.e., respectively, GSSG and CySS] (1, 2) and that their plasma concentrations are substantially displaced from cellular values (3) has significantly altered concepts of oxidative stress (4, 5). For example, the in vivo “balance” of pro-oxidants and antioxidants cannot be defined by any single entity, such as an equilibrium constant, and our growing knowledge of signaling mechanisms indicates that oxidative stress may be better defined as a disruption of redox signaling, rather than as an imbalance of pro-oxidants and antioxidants. The failure of large-scale, double-blind interventional trials with free-radical scavenging antioxidants may likewise reflect an oversimplified therapeutic approach.”

If you have too many oxidants/oxidative stress in your system, you should just add antioxidants to restore the balance of oxidants and antioxidants, right?  Well, it’s not that simple.  Once the signaling mechanisms within mitochondria start the process of oxidative stress and apoptosis (programmed cell death), you can’t stop the process or repair the damage by adding more antioxidants to the mix.  If it was as simple as a disruption in the balance between oxidants and antioxidants, we would all be cured by glutathione drips and vitamin C supplements.  Unfortunately, there are complex feedback loops that make the process much more difficult to fix than that.  I’m not saying that glutathione drips and vitamin C supplements aren’t worth a try, it’s just that adding antioxidants to make up for the excess of oxidative stress (in the form of Reactive Oxygen Species and Reactive Nitrogen Species) is an oversimplified approach.

“Cells that overexpress the mitochondrion-specific thioredoxin Trx2, however, have been found to be resistant to tBH-induced loss of mitochondrial membrane potential and apoptosis”

Mitochondrion-specific thioredoxin Trx2 (http://en.wikipedia.org/wiki/Thioredoxin) is protective.  I’m not sure exactly what the implications of this are, but I suspect that those of us who got “floxed” have low levels of mitochondrion-specific thioredoxin Trx2.  (We probably are deficient in cellular magnesium and have a genetic predisposition toward susceptibility to mitochondrial injury and oxidative stress too.)


“Mitochondrial Trx2 responds to changes in the extracellular redox potential of Cys/CySS (http://en.wikipedia.org/wiki/Cysteine) (EhCys/CySS) over a range that is relevant to cardiovascular disease in humans.” and “Previous in vitro findings support a cause–effect relationship for plasma CySS in cell signaling pathways associated with cardiovascular disease.”

Cardiovascular disease is related to mitochondrial function and oxidative stress / antioxidants.

Every chronic disease that plagues humans has its roots in mitochondrial dysfunction.  That may be Lisa’s theory, or it may be the truth.  TBD.  But there are enough journal articles noting how mitochondria relate to all sorts of chronic diseases that you’d think that our regulatory agencies would require that the effects of pharmaceuticals on mitochondria be tested before they are released to the market.  But no, they don’t.  They’re incompetent fools.  And because of their foolishness the pharmaceutical companies really have gotten away with creating customers, not cures.

“Mass spectrometry-based redox proteomics show that several classes of plasma membrane and cytoskeletal proteins involved in inflammation respond to this redox switch (Trx2), including vascular cell adhesion molecule, integrins, actin, and several Ras family GTPases.”

This really cryptic, difficult to understand sentence may actually say a lot about FQ toxicity.  The Trx2 redox switch (http://en.wikipedia.org/wiki/Thioredoxin) is protective against loss of mitochondrial membrane potential and apoptosis (see above).  So, perhaps underexpression of the Trx2 redox switch  leads to inflammation of  vascular cell adhesion molecules, integrins, actin, and several Ras family GTPases.  What are these things, you ask?  Wiki will tell us!

Vascular Cell Adhesion Moleculeshttp://en.wikipedia.org/wiki/VCAM-1 – “The VCAM-1 protein mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also functions in leukocyte-endothelial cell signal transduction, and it may play a role in the development of atherosclerosis and rheumatoid arthritis.” (I’ll let you look up all of the words you don’t know in this – ugh.)

Integrins http://en.wikipedia.org/wiki/Integrin and http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/CellAdhesion/integrinfunction.htm – “Integrins are cell-surface receptors that mediate cell-cell adhesion and are of great importance in binding and interactions of cells with components of the extracellular matrix (ECM) such as fibronectin (and cell-matrix). Importantly, integrins facilitate “communication” between the cytoskeleton and extracellular matrix, allowing each to influence the orientation and structure of the other.”  When your integrins are messed up, your cytoskeleton can get messed up.  Or something like that.

Here is an about how fluoroquinolones that mentions how they relate to integrins –

http://intl-vet.sagepub.com/content/38/2/143.full – “Lack of extracellular Mg2+ impairs the function of integrins.  These transmembrane proteins connect the cells to extracellular matrix”  This stuff has something to do with how fluoroquinolones mess up tendons.  Yeah.

Actinhttp://en.wikipedia.org/wiki/Actin  It’s important for cellular function.  (That’s all I’ve got for you – read the wiki :p )

Ras Family GTPases – http://en.wikipedia.org/wiki/GTPase  It’s important for cellular function.  (That’s all I’ve got for you – read the wiki :p )

You could get completely lost looking up all of the different systems described within this sentence.  Now that I have dug through it, maybe the authors of the study stated things as succinctly as possible.  This stuff is hard.

If someone significantly smarter than me wants to figure out how each of these cellular functions relate to magnesium, and, of course, floxing, that would be great.

Chelatable Iron, Oxidative Stress, and Cell Death

This whole section is about how iron relates to drug induced liver injury (DILI).  I’m not going to go over it piece by piece.  One thing that makes me curious about this section is that iron helped me to feel better than any other supplement.  I wonder why that is.  If the answer is in the article, I don’t understand chemistry well enough to get it from the article.

“In the mitochondrial permeability transition (MPT), high-conductance permeability transition (PT) pores open that make the mitochondrial inner membrane nonselectively permeable to all solutes of molecular mass up to approximately 1500 Da (59, 60). Calcium ion, oxidative stress, and numerous reactive chemicals induce onset of the MPT, whereas cyclosporin A (CsA) and pH less than 7 inhibit pore opening. After MPT onset, mitochondrial depolarize and undergo large-amplitude swelling driven by colloid osmotic forces, which are the hallmarks of the MPT. Swelling leads to rupture of the mitochondrial outer membrane and release of proapoptotic cytochrome c and other factors from the intermembrane space.”

Calcium + oxidative stress = apoptosis.  I’ve seen this elsewhere – https://floxiehope.com/2013/12/17/article-breakdown-mitochondrial-reactive-oxygen-species-control-t-cell-activation-by-regulating-il-2-and-il-4-expression-mechanism-of-ciprofloxacin-mediated-immunosuppression/

Interplay of Signal Transduction and Mitochondria in the Acetaminophen model

This section goes over how acetaminophen causes mitochondrial damage and drug induced liver injury.  It’s not a one-step process – it’s really complex and multiple things have to go wrong, at a cellular level, at once.  But it can happen.

As I mentioned above, I hypothesize that pharmaceutical induced mitochondrial injury is the cause of most chronic diseases.  Per Dr. Richard Boles, an expert in mitochondrial dysfunction and diseases:

these are partial defects. Mitochondrial dysfunction doesn’t really cause anything, what it does is predisposes towards seemingly everything. It’s one of many risk factors in multifactorial disease. It can predispose towards epilepsy, chronic fatigue, and even autism, but it doesn’t do it alone. It does it in combination with other factors, which is why in a family with a single mutation going through the family, everyone in the family is affected in a different way. Because it predisposes for disease throughout the entire system.”  (http://www.hormonesmatter.com/cyclic-vomiting-syndrome-mitochondrial-dysfunction/)

Is acetaminophen causing mitochondrial damage???  Is it damaging or depleting mtDNA?  Is that damage hereditary????  Because if ACETAMINOPHEN is leading to a variety of chronic diseases, ugh, well, we might just be fucked (sorry, I couldn’t think of another word for the situation).

Fluoroquinolones deplete mitochondrial DNA content – “Interestingly, as an inhibitor of bacterial topoisomerase II and an inducer of DNA double-strand breaks, ciprofloxacin was also shown to deplete the mitochondrial DNA (mtDNA) content, thus leading to mitochondrial dysfunction and retarded cellular growth (15–17).” http://www.jimmunol.org/content/184/9/4827.full.pdf  Awesome, huh?

I think that fluoroquinolone induced mitochondrial damage, both direct and hereditary, is responsible for the increase in every chronic disease that has increased in prevalence along with fluoroquinolone use.

“One of the most striking and puzzling clinical hallmarks of idiosyncratic (host-dependent) DILI is the delayed onset of the disease. In fact, the time between initiation of daily drug treatment and the presentation of biochemical markers and clinical symptoms of liver injury can vary from a few weeks to several months, sometimes even exceeding a year (89). The reason for the long lag, often followed by an abrupt progression to DILI, is currently not known. However, it is clear, for the vast majority of drugs, that the delayed time to onset is not related to a gradual accumulation (of drug or drug metabolite) that would eventually lead to critical and toxicologically relevant concentrations in the liver. Instead, the lag time could be explained by an accumulating effect of a drug. This notion, together with experimental findings, is in line with the concept that mitochondria are involved in the etiology of DILI, because damage to mitochondria often reflects successive chemical insults, such that no immediate cause for functional changes or pathological alterations can be established. There is indeed experimental evidence that prolonged injury to mitochondria, such as that which typifies oxidative injury to mitochondrial DNA or to components of the electron transport chain (ETC), has to cross a certain threshold (or a number of thresholds) before cell damage or cell death becomes manifest (Figure 4A).”

Underlining added by Lisa.  This paragraph explains both delayed reactions and the fact that most people have a tolerance threshold for fluoroquinolones.  If your doctor, or anyone else, tells you that your reaction that came months after you stopped administration of a fluoroquinolone “couldn’t have happened because of the FQ, because it was metabolized already,” or something like that, tell him or her to read this paragraph as many times as it takes to understand it.  Damage to mitochondria, whether related to DILI or not, is not linear and it is not (necessarily) immediate.  Unfortunately, this is not understood by anyone other than the authors of this study, and probably a few other scientists, so suing based on a delayed reaction to a drug that you have tolerated well in the past is difficult to impossible.

“This non-linear response can be explained upon consideration that the molecules that subserve mitochondrial function (e.g., mitochondrial DNA, mRNA, and ETC proteins) are present in excess of amounts required for normal cell function. This reserve (or buffering) capacity acts as a protective mechanism; however, at a certain stage of damage, the supply of biomolecules needed to support wild-type mitochondrial function becomes compromised.”

For each of us Floxies, the reserve capacity of our mtDNA has been depleted.  I have no clue if it can be built up again or not.

“a number of human mitochondrial genetic diseases that are clinically discreet are being diagnosed at unexpected rates”

It is REALLY IMPORTANT that it be determined whether or not pharmaceutical induced damage to mitochondria is hereditary.  Seriously scientists – important stuff – answers will be greatly appreciated.

“First, all the investigated drugs (including trovafloxacin, a fluoroquinolone) invariably decreased the activity of key mitochondrial proteins that are sensitive to oxidant stress (e.g., aconitase-2, complex I) and often decreased the expression of mitochondrial (but not nuclear) genes (120). Second, we found that these markers of mitochondrial injury became apparent only after four weeks, although a number of cytoprotective pathways were activated within two weeks. It thus appears that an initial adaptive response was followed by a toxic response (121), possibly also involving a threshold.”

What happens when expression of mitochondrial genes are decreased?  What are the implications of this finding?

The fact that there is an initial adaptative response followed by a toxic response (to pharmaceutical induced mitochondrial injury) may explain why there are so many different results to studies of fluoroquinolones (and other mito damaging drugs).  Long-term studies need to be done.  Studies that take into consideration that delayed reactions occur, need to be done.  Studies that take into consideration tolerance thresholds need to be done.  Please.

“First, superoxide that escapes dismutation to hydrogen peroxide cannot cross the inner mitochondrial membrane and can oxidize [Fe-S]-containing enzymes (e.g., aconitase and complex I/III subunits). Alternatively, superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−). For example, the fluoroquinolone antibiotic trovafloxacin (TVX), a typical DILI-associated drug, raises steady-state levels of NO in hepatocellular mitochondria (unpublished data). The mechanisms are not known, but TVX also increases cytosolic (non-ferritin-bound) Ca2+, likely activating the Ca2+-dependent mitochondrial NO synthase (123) to produce ONOO−. Peroxynitrite is dangerous for a number of reasons: i) under acidic conditions, it can be degraded to form the extremely reactive hydroxyl radical; ii) it may directly cause the nitration of aconitase, Sod2, and the [Fe-S]-containing subunits of ETC complexes; and iii) it can induce mitochondrial permeabilization (Figure 4B) (124). This superimposed oxidative/nitrative stress could ultimately push the cell across the threshold to observable injury.”

Floxies – that’s what happened to you (and me).  It’s really hard to understand, I know.  I have a headache right now and I’m guessing that you do too if you’ve gotten this far in the post.  It’s important information though.

On a light note, I think that it’s funny that fluoroquinolones convert “NO” into “ONOO” in our cells.  Yup, that’s about what it feels like – “no” turning into “oh no” turning into “oh fuck” which turns into “fuck you Bayer / Johnson & Johnson.”  🙂

The end of the article and my comments.

Dean P. Jones, John J. Lemasters, Derick Han, Urs A. Boelsterli and Neil Kaplowitz are brilliant.  I thank them very much for this article.  It answers a lot of questions.  It still leaves many unanswered, of course – as any good article does.  I hope that they, and more scientists, are doing more work on the relationship between pharmaceutical induced mitochondrial injury and disease states.
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Fluoroquinolone Caused Mitochondrial Damage and Oxidative Stress – What are the Consequences for Floxies?

I’m working on a couple of posts/articles/essays right now about how all sorts of chronic diseases, from diabetes to alzheimer’s to autism, are caused by mitochondrial damage and oxidative stress.  I’m pointing out that pharmaceuticals cause mitochondrial damage and oxidative stress.  Of course, I’m focusing on my least-favorite pharmaceuticals, fluoroquinolones, and am trying to make a case that fluoroquinolones cause many chronic diseases.

That line of thinking is scary as hell for those of us who have had a bad reaction to a fluoroquinolone.

What does the connection between fluoroquinolone induced mitochondrial damage / oxidative stress and chronic diseases mean for us?  What is our prognosis?  Are we going to come down with diabetes or Alzheimer’s?  Are our kids going to be autistic?  Scary stuff – aaaarghhhh!!!  New plan – run and hide on a tropical island far from the internet.

Just so you all know, I’m not sure what it all means.  I am doing my best to put together the pieces of the puzzle.  I’m doing my best to draw conclusions from reputable sources.  I’m doing my best to understand what happened in my body when the Cipro bomb went off in me.  In trying to understand what happened, I’m stumbling upon articles that point to the possibility that the problem is bigger than we think.  It is possible that fluoroquinolones are causally related to fibromyalgia, chronic fatigue syndrome / M.E., all autoimmune diseases, depression, anxiety, bipolar disorder, diabetes, Alzheimer’s, autism, some kinds of cancer, and more.  Are all cases of those chronic diseases caused by fluoroquinolones?  Of course not – most of the diseases are older than fluoroquinolones.  But it’s possible that they have increased hand in hand with fluoroquinolone use because of the damage that fluoroquinolones do to mitochondria, and the oxidative stress that they induce.

It’s also possible that other drugs are the primary culprits.  And I suppose that it’s even possible that junk food that is full of free radical producting chemicals is the culprit behind all the oxidative stress that people who have chronic diseases experience.  Or maybe the problem is GMO corn or childhood vaccines or pesticides or something else.  There are pretty reputable sources that note that pharmaceuticals cause mitochondrial damage and oxidative stress though, so I’m betting that the culprits are Bayer, Johnson & Johnson, Merck, Pfizer, Abbvie and all the other pharmaceutical giants that are very good at making customers and very bad at actually promoting health.

Anyhow, the theory that fluoroquinolones cause mitochondrial damage / oxidative stress and that mito damage / oxidative stress are behind all sorts of chronic diseases is the theory that I’m going with.  Whether I’m right or wrong is yet to be seen.  Even though my theory may scare the crap out of you, your support is still greatly appreciated.  🙂

If I’m wrong, the case against fluoroquinolones is still pretty damning.  With fluoroquinolones, one can convert an acute problem, an infection, into a chronic syndrome that includes destruction of connective tissue (tendons, ligaments, cartilage, fascia, etc.) throughout the body, damage to the nervous systems (central, peripheral and autonomic), and more.  Fluoroquinolone toxicity can develop slowly or quickly.  It can last for months or years.  Tragically, some people don’t recover.  But most people do – with time.

How fluoroquinolones cause the damage that they do is hugely complex and difficult to understand.  Part of the damage mechanism is mitochondrial damage and oxidative stress, hence the trip down chronic disease lane.  Other aspects of how fluoroquinolones work – DNA adducts, RNA transcription errors, disruption of tubulin assembly, etc. are equally daunting and potentially harmful.  Ugh.  Bad news.

But people do recover from fluoroquinolone toxicity.  I did.  I’m fully recovered.  So are the other people who have shared their stories on www.floxiehope.com.  I wonder if the chronic disease prognosis for those who recover is any different from the prognosis for those who don’t, or for those who take fluoroquinolones but don’t have an adverse reaction.  I don’t think that a study to answer that question has been done.  It would be interesting to find out the answer.

Right now, we don’t know the answers though, so we have to make assumptions about our health and our future.  If you’re going to make baseless assumptions about your personal health prognosis though, they may as well be hopeful ones.  Try to believe that you will heal and that once you heal you will be as capable, resilient and durable as you were before a fluoroquinolone knocked you down.  Or, better yet, believe that floxing gave you some sort of health super-powers.  Here is a crazy thought – what if our floxing reaction was actually protective against damaged cells and the conversion of those cells into chronic diseases?  What if our horrible reaction was because of mass apoptosis (programmed cell death), and in dying, those cells kept from reproducing and leading to a chronic disease at some later time?  Now that is a far-fetched hypothesis, but I kind of like it.  I just hope that my recovery doesn’t mean that my bad cells are sticking around now.  :p

Back to fluoroquinolones being related to the chronic diseases – what if I’m right?  What if fluoroquinolone caused mitochondrial damage and oxidative stress is behind all of the chronic diseases of modernity?  Well, it’s a sad state of affairs.  But people should know about it.  They should hear about it.  They have the right to know.

But you are going to be fine.  Try to believe it.


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Article Breakdown – “Mitochondrial Reactive Oxygen Species Control T Cell Activation by Regulating IL-2 and IL-4 Expression: Mechanism of Ciprofloxacin-Mediated Immunosuppression”

I’ve read this article 14 times. I think that I understand it. It’s not an easy article to read. Actually, it’s a beast. I’m going to go over what I think are the interesting points of the article in this post. I’m also going to go over something that I think the researchers got wrong, and the implications of their false (IMO) conclusion.

Here is the article –


Mitochondrial Reactive Oxygen Species Control T Cell Activation by Regulating IL-2 and IL-4 Expression: Mechanism of Ciprofloxacin-Mediated Immunosuppression

The Journal of Immunology, 2010, 184: 4827–4841.

Marcin M. Kamin´ ski,* Sven W. Sauer,† Claus-Detlev Klemke,‡ Dorothee Su¨ ss,*

Ju¨rgen G. Okun,† Peter H. Krammer,* and Karsten Gu¨low*

There is a lot of phenomenal information in the article, but I’m going to go over what I think they got wrong first. The researchers found that Ciprofloxacin had an immunosuppresive effect on T-cells, inhibited the production of ROS (Reactive Oxygen Species) and were anti-inflammatory. I don’t think that this is correct. Some of the results discussed in the paper, that I will go over later in this post, note that the effect of Ciprofloxacin on T-cells is one of activation of immune responses, not suppression. More on that later. As for the production of ROS, there are multiple peer-reviewed articles that note that fluoroquinolones (Ciprofloxacin and others) increase the production of ROS. Here are a few –




There are hundreds more.

I have no reason to doubt the intelligence, motives or methods of the Researchers who conducted this study, so why did they get a result that is the opposite result from most other Researchers? I’m not sure of the answer, but I think that it may have something to do with the fact that the cells that they studied were cultured in uridine. Supplementation of uridine, as well as consuming foods that have uridine in them, have seemed to help Floxies. Because of this, I wonder if uridine counteracts the production of ROS, and thus the results of the study were skewed. There may be a completely different answer for why the researchers who wrote the study that I’m reviewing concluded that ROS decreases with Ciprofloxacin, and all other researchers who have looked at the topic note that fluoroquinolones increase ROS production, but I think that the uridine direction is an interesting path. It leads to acyl glucuronidation and other headache inducing topics.

Anyhow, they got that wrong (as shown by the multiple articles that state the FQs increase ROS, not decrease it, not because I say so), so all conclusions based on the premise that fluoroquinolones decrease ROS or oxidative stress, should be disregarded. However, they still said some really interesting stuff about the effects of Ciprofloxacin on the cell.

Before I go into the good stuff from the article, I’m going to express my annoyance over the following paragraph:

Ciprofloxacin, as well as other members of the fluoroquinolone group of antibiotics, is characterized by immunomodulatory properties of an unknown mechanism. The effects of ciprofloxacin on T cell activation-induced gene expression remain vague. Numerous conflicting reports stated that ciprofloxacin activates or inhibits T cell activation-induced gene expression (e.g., for IFN-g, TNF-a, IL-2, and IL-4) (11–14).”

If a drug has immunomodulatory properties, perhaps it’s a good idea to figure out the mechanism. If more than 20 million prescriptions of these drugs are going to be given out each year in the U.S. Alone, perhaps it is a good idea to figure out the mechanism for how they effect the human immune system.

The effects of Ciprofloxacin on gene expression may be vague, but researchers recently found that another topoisomerase interrupter, Topotecan, triggered the expression of Autism related genes. So “vague” has consequences and they may not be pleasant ones.

“Conflicting reports?” Welcome to my world. But it really bothers me that Scientists can’t determine the direction of the arrow. It’s not a judgment call. It’s not a matter of opinion. It should be a matter of fact. How does Ciprofloxacin effect T-cell activation-induced gene expression? This should be a testable question.

Now onto the highlights:

Interestingly, as an inhibitor of bacterial topoisomerase II and an inducer of DNA double-strand breaks, ciprofloxacin was also shown to deplete the mitochondrial DNA (mtDNA) content, thus leading to mitochondrial dysfunction and retarded cellular growth (15–17).”

Why is this stuff on the market? Oh yeah, because the FDA systematically ignores the effects of drugs on mitochondria. Here is an article about how this is the case for many drugs: http://psychrights.org/Research/Digest/NLPs/DrugsCauseMitochondrialDamage.pdf

In this article, we show that prolonged ciprofloxacin treatment of preactivated human T cells leads to a loss of mtDNA content. This was accompanied by impaired activity of the mtDNA-encoded mitochondrial enzymes, such as complex I, whereas the activities of the nuclear-encoded mitochondrial enzymes, complex II (succinate dehydrogenase) and citrate synthase, were unaffected.”

I’m pretty sure that loss of mitochondrial DNA (mtDNA) content is bad.

Because complex I is central to energy production in the cell, its malfunction results in a wide range of neuromuscular diseases.” (http://www.mrc-mbu.cam.ac.uk/research/mitochondrial-complex-i) Does the finding that Ciprofloxacin impairs complex 1 mean that Ciprofloxacin can cause neuromuscular diseases? I’m pretty sure that most Floxies would sadly say, “It sure does!”

Per http://www.ncbi.nlm.nih.gov/gene/51103, “Complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane.” Basically, this is an explanation as to how glutathione is massively depleted by fluoroqinolones (FQs). The FQs impair mitochondrial enzyme complex 1 which is responsible for the production of ubiqunone (coenzyme Q) which is responsible for the production of glutathione. This finding is also consistent with an increased production of ROS, not a decrease in ROS. Antioxidant production is inhibited because Complex 1 is inhibited – therefore an increase in ROS would make sense. 

Thus, the current study demonstrates for the first time that mitochondrial complex I-derived ROS control T cell activation.”

Does it mean that mitochondrial complex 1 damage has something to do with autoimmune diseases? It certainly means that it’s REALLY IMPORTANT that it be correctly determined whether Ciprofloxacin (and other fluoroquinolones) increase or decrease ROS production. As I noted above, all other studies that I found said that ROS increases with administration of fluoroquinolones.

Ciprofloxacin treatment was shown to exert various effects on activation- induced gene expression in T cells (10). Stimulatory effects of immediate ciprofloxacin treatment (incubation time up to 72 h) on basal expression of IL-2, TNF-a, or IFN-g in mitogen-activated T cells have been reported (11, 12, 24).”

Stimulating the expression of IL-2, TNF-a and IFN-g is really bad news. Basically, if those are stimulated, an autoimmune-disease, or at least an autoimmune-disease-like state, will ensue. IL-2 is a protein signaling molecule found in the immune system – especially white blood cells. TNF-a is Tumor Necrosis Factor (a) and it also regulates immune system cells. It should be noted that drugs that are used to fight autoimmune diseases are TNF inhibitors. Enbrel and Humira work by suppressing the expression of TNF. If Ciprofloxacin (and other fluoroquinolones) increase the expression of TNF, well, they will induce an autoimmune-disease-like reaction, if not an actual autoimmune disease. IFN-g is interferon gamma, it’s a protein signal that is critical for the operation of the immune system. Again, over-stimulating it is probably a bad idea – unless an autoimmune disease is the goal.

To be fair, it should be noted that the Researchers who authored this particular study did not find that Ciprofloxacin had a stimulatory effect on T-cells. Rather, they found that, “Ciprofloxacin treatment led to a moderate increase in basal IL-2 and -4 expression levels in PHA-preactivated T cells (Fig. 1A). However, prolonged ciprofloxacin treatment clearly inhibited anti-CD3–induced IL-2 and -4 expression in a dose-dependent manner (Fig. 1B).”

They also found that:

Ciprofloxacin treatment induces mtDNA loss, impairs mitochondrial function, and inhibits cellular growth in cultured preactivated human T cells.” (Italicization and emphasis added by them.)

What are the consequences of mtDNA loss? What are the consequences of impairment of mitochondrial function? What are the consequences of inhibiting cellular growth in human t-cells? These are questions that should be asked. The questions should be asked both for the subject human that has consumed the damaging drug and intergenerationally. After all, we are talking about DNA.

In addition, ciprofloxacin induced mtDNA depletion in cultured PHA-preactivated T cells by up to 50%, as estimated by real-time PCR analysis (Fig. 1E). Moreover, mtDNA loss resulted in an impairment of mitochondrial function. This is reflected by significantly decreased activity of the mtDNA-encoded respiratory complex I (Fig. 2A).”

This is a partial answer to the questions about the consequences of mtDNA depletion. What are the consequences of impairing mitochondrial function? What are the consequences of decreasing activity of the mtDNA encoded respiratory complex 1? (Again, I question the result of “decreasing” the activity – it might increase it – there are so many conflicting reports that it’s just obnoxious.)

Genes located on mtDNA encode crucial components of the mitochondrial ETC, such as complex I, III, and IV and ATP synthase. Thus,the loss of mtDNA results in a decreased activity of the ETC (25).”

ETC is the electron transport chain – the process through which mitochondria create energy. Decreasing mtDNA and the activity of the ETC doesn’t seem like a very good idea. What are the consequences of doing so? It doesn’t seem like an unreasonable question to ask.

This indicates that the IL-2 and -4 promoters depend on the simultaneous presence of the increased cytosolic Ca2+ concentration and the PMA-induced oxidative signal. Selective blocking of ROS (with the antioxidant NAC) and the Ca2+ influx (with the intracellular Ca2+ chelator BAPTA-AM) (Fig. 4A, 4C) led to a significant inhibition of IL-2 and -4 promoter activities (Fig. 4B, 4D).”

If one assumes that Ciprofloxacin is a promoter of IL-2 and IL-4 (the opposite of the conclusion of the Researchers, it should be noted, – but I really think that they got the direction of the arrow as to the effect of fluoroquinolones on immune system cells wrong – and my thinking this is backed up by other studies), does this mean that a combination of too much Ca2+ (calcium) and ROS (oxidative signal) within our bodies was part of the equation that made us have the reaction that we had (getting Floxed)? If so, would a combination of NAC as an inhibitor of ROS, combined with a calcium chelator be a cure if applied early on?

I also interpreted this as meaning that Floxies should avoid calcium, but I’m not sure about that.

The immunomodulatory properties of ciprofloxacin and other drugs of the fluoroquinolone group are well documented (10). Most of the in vitro studies showed stimulatory effects of immediate or short-term (up to 72 h) ciprofloxacin treatment on basal gene expression in peripheral mitogen-preactivated human T cells (11, 12, 24). However, several in vitro and in vivo studies suggested that ciprofloxacin has inhibitory properties toward T cell activation (10, 13, 14, 28). In addition, in vitro experiments demonstrated that prolonged ciprofloxacin treatment retards cellular growth (25). This cytostatic effect is mediated by inhibition of the putative mitochondrial topoisomerase II in proliferating cells, resulting in a gradual mtDNA loss and energy shortage (16, 25). Our previous work showed that the mitochondria-generated oxidative signal, in the form of H2O2, is indispensable for T cell activation induced expression of CD95L, a crucial AICD mediator (9). Thus, it is important to clarify whether ciprofloxacin-induced mitochondrial dysfunction could account for differential effects of ciprofloxacin on activation-induced gene expression in T cells.”

This paragraph is both interesting and infuriating because it is abundantly clear that too little is known about these drugs.

The last sentence in the paragraph is interesting. It makes me wonder, do the effects of Ciprofloxacin and other fluoroquinolones depend on which genes are activated/depressed and how t-cell gene expression is influenced (and it’s influenced differently in different people)? Perhaps in some cases/people, genes that inhibit the immune system are expressed, but in other cases/people, genes that stimulate the immune system are expressed. Fluoroquinolones adduct to DNA (http://www.jbc.org/content/273/42/27668.full). Maybe where the quinolone molecule inserts itself into the DNA makes the difference between inhibition and stimulation of the immune system. That could also be an explanation as to why there are such dramatically differing results from study to study. These drugs don’t influence all cells in the same way – making scientific experimentation and conclusions difficult. But if these drugs were looked at from the perspective of being DNA adducts, perhaps the mysterious discrepancies in results could be explained.

Our previous work demonstrated that in the case of CD95L expression, the IP3/Iono induced Ca2+ signal is complemented by a DAG/PMA-induced H2O2 signal. The combination of a mitochondria-generated H2O2 signal with a simultaneous Ca2+ influx into the cytosol constitutes the minimal requirement for induction of CD95L expression (8).”

CD95L is a transmembrane protein that belongs to the TNF family and induces apoptosis – programmed cell death.

Fluoroquinolones have been repeatedly shown to induce apoptosis. This paragraph again makes me think that calcium is an important part of the equation of Floxing. Perhaps it is part of what makes the apoptosis occur.

However, the ability of ciprofloxacin to induce delayed-type hypersensitivity via direct TCR triggering (51) may pose difficulties to the topical application of ciprofloxacin to alleviate skin inflammation.”

The acknowledgement of “delayed-type hypersensitivity via direct TCR (t-cell receptor) triggering” is important.

Applying Ciprofloxacin to the skin in order to reduce inflammation is a dumb idea for multiple reasons, one of which being that the microbiome on the skin is really important and disturbing it by killing all the bacteria on the skin is a really bad idea. Also, an adverse reaction to the Ciprofloxacin can induce more inflammation.

Furthermore, it was demonstrated that the malfunctioning of complex I leads to excessive generation of ROS (54). Thus, it seems interesting that Leber hereditary optic neuropathy, caused by deficient function of mitochondrial respiratory complex I, is often associated with T cell-mediated autoimmune multiple sclerosis-like syndrome (55).”

Cipro leads to the malfunctioning of complex 1 which leads to excessive generation of ROS.

Perhaps Floxies should ask their Rheumatologists if they have T-cell-mediated autoimmune multiple sclerosis-like syndrome.

This article has some really interesting points, that’s why I’m dissecting it, but the internal inconsistency within the article is annoying to say the least. Which direction do the arrows go? Does Cipro lead to an increase in ROS or not? Answer – of course it does. But this article concludes otherwise, despite statements like the direct quote above.

In addition, recent epidemiologic studies on a cohort of patients with mitochondrial disorders showed a high statistical association between these pathologies and lymphoid malignancies (56).”

Insert profanity here.

Written by me for another post that has yet to be published, “Destruction of mitochondrial DNA can result in mass apoptosis. When this occurs, an autoimmune-disease-like reaction can occur (14). However, if cell damage occurs but the cell does not die, but rather replicates the DNA errors, cancer can result (30, 31). Additionally, drugs that inhibit CYP450 liver enzymes leave people more susceptible to cancer-causing pathogens (32) and fluoroquinolones inhibit CYP450 enzymes (8, 33). How ironic, isn’t it? Cancer can result from DNA damaging drugs that, when used in doses that cause apoptosis, can be chemotherapeutic (and have all of the drawbacks of chemotherapy drugs).”

To explore how mitochondrial damage effects cells, the researchers compared the effects of Ciprofloxacin to the effects of Rotenone (Rot), a pesticide, insecticide and piscicide. http://en.wikipedia.org/wiki/Rotenone That should at least imply something.

I am not a Scientist. I am not an expert in mitochondria, cellular function, autoimmune diseases or anything else. However, I have experienced being floxed and I have been doing research on the topic of fluoroquinolone toxicity for the past 2 years. I’m sure that doesn’t count for much, but I think that I’m right in my assessment of the article reviewed above. (Of course I do, I wouldn’t have written what I wrote if I didn’t think I was right – but I could still be wrong – it has happened.) I encourage you to read the article yourself – preferably multiple times because it really is a beast of an article. I hope that this post clarified things and that it didn’t make you glaze over completely.

Fluoroquinolones are damaging human mitochondria. Though I disagree with the researchers who authored this study about the effects of fluoroquinolones on ROS and inflammation, they do note much of what fluoroquinolones can do to mitochondria and mtDNA. The consequences of damaging mtDNA are yet to be determined. I hope that they’re not too catastrophic.

Thank you for reading Floxie Hope!  I hope that all who read Floxie Hope gain insight, support, understanding and, most of all, HOPE.  If you would like to support Floxie Hope, all contributions will be greatly appreciated!  Click HERE to contribute to Floxie Hope.  Thank you!

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