Study Finds that Ciprofloxacin Depletes Mitochondrial DNA

DNA replication fluoroquinolone Topoisomerase Interrupter

This post contains quotes from the article “Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in Ciprofloxacin-Treated Mammalian Cells” that was published in Molecular Pharmacology in 1996.  It’s a good article.  It’s an interesting and damning article.  It’s a difficult article.  It would be nice if more people read it, and I wish that its implications were better understood and explored by research scientists and regular people alike.

Direct quotes from the article are in bold and italicized.  My commentary follows each quote.

“The loss in mtDNA was associated with a delayed loss in mitochondrial function. Here, we report that the 4-quinolone drug ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concentrations that deplete cells of mtDNA.”

Ciprofloxacin depletes mitochondrial DNA in mammalian cells.  It’s right there in black and white.  I have no idea why it didn’t strike anyone as alarming when it was published in 1996.  It sure is alarming now.

It should be noted that, “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.” (source)  And that mitochondrial damage is linked to “symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness.” (source)  Mitochondrial dysfunction has been linked to multiple diseases of modernity including autoimmune diseases, neurodegenerative diseases, autism and “mysterious” diseases such as fibromyalgia and ME/CFS.

Also, as I’ve pointed out before, the FDA has noted in their internal documents that fluoroquinolones are toxic to mitochondria, and that mitochondrial damage is linked to many diseases, including neurodegenerative diseases.  More information about that can be found in the post, “FLUOROQUINOLONE ANTIBIOTICS DAMAGE MITOCHONDRIA – FDA DOES LITTLE

“Resistance was not due to a decrease in cellular drug accumulation, suggesting that ciprofloxacin cytotoxicity is caused by the loss of mtDNA-encoded functions.  Analysis of mtDNA from ciprofloxacin-treated cells revealed the presence of site-specific, double-stranded DNA breaks.”

Consequences?  Implications?  What happens when cytotoxicity is induced by DNA breaks?

“These results suggest that ciprofloxacin may be causing cytotoxicity by interfering with a mitochondrial topoisomerase Il-like activity, resulting in a loss of mtDNA.”

Many assert that fluoroquinolones only affect bacterial topoisomerases.  It turns out that mitochondrial topoisomerases are affected too.  Fluoroquinolones should be used as prudently and cautiously as all other topoisomerase interrupting drugs.  All the other topoisomerase interrupting drugs are chemo drugs that are only used to treat cancers.  To prescribe a drug that depletes mitochondrial DNA and affects human topoisomerases in order to treat urinary tract infections and traveler’s diarrhea is absurd, short-sighted and wrong.

It should also be noted that, “Our data suggest that chemicals or genetic mutations that impair topoisomerases, and possibly other components of the transcription elongation machinery that interface with topoisomerases, have the potential to profoundly affect expression of long ASD (autism spectrum disorder) candidate genes. Length-dependent impairment of gene transcription, particularly in neurons and during critical periods of brain development, may thus represent a unifying cause of pathology in many individuals with ASD and other neurodevelopmental disorders.” (source)

The team of scientists who wrote that last quote are looking at whether or not fluoroquinolones turn on genes that are related to autism.  The results of their exploration have not yet been published.

What is known though, is that topoisomerases are really important.  Duh–they’re the enzymes responsible for proper DNA and RNA replication—did someone think they were optional?  Interrupting topoisomerases with drugs is a really, really, really bad idea.

“Studies have also suggested that 4-quinolones may interfere with cell growth by inhibiting mammalian mtDNA replication (6, 11). Castora et al. (11) found that the 4-quinolone drugs nalidixic acid and oxolinic acid inhibited mtDNA replication in isolated rat liver mitochondria. These investigators inferred that this effect might be mediated by the inhibition of a mitochondrial topoisomerase II activity related to the bacterial enzyme DNA gyrase.”

Naladixic acid is the backbone of all fluoroquinolone antibiotics.  The quote speaks for itself.

 “We recently demonstrated that the 4-quinolone drugs nalidixic acid and ciprofloxacin cause a selective loss of mtDNA in drug-treated mammalian cells (6). The loss of mtDNA was associated with a decrease in mitochondrial respiration and an arrest in cell growth. These results suggested that inhibition of mammalian cell proliferation by 4-quinolone drugs might be caused by the selective depletion of mtDNA, resulting in compromised mitochondrial activity. We now report that ciprofloxacin causes a delayed cytotoxicity in cultured mammalian cells at concentrations that deplete cells of mtDNA.”

DELAYED CYTOTOXICITY!  When someone says that you “shouldn’t” be experiencing an adverse reaction to a fluoroquinolone weeks, months or even years after you took the drug, show them this.  Delayed cytotoxicity and mtDNA depletion–they’re right there.  Fluoroquinolones are NASTY drugs.  Why they are used frivolously is beyond my comprehension.

“We previously demonstrated that ciprofloxacin induces a selective depletion of mtDNA in mammalian cells. The depletion of mtDNA preceded a decrease in mitochondrial respiration and cell growth, suggesting that mtDNA was a primary target of drug action (6). Studies have recently shown that some cultured mammalian and avian cells can survive in the absence of mtDNA-encoded functions if the growth medium is supplemented with pyrimidines, pyruvate, and elevated concentrations of glucose (21-23). Cells deficient in mtDNA rely exclusively on glycolysis for energy.”

Hmmmmm…. So do our cells need/want more glucose??

And, again, I’d like to point out the clearly stated, “ciprofloxacin induces a selective depletion of mtDNA in mammalian cells.”

fluoroquinolone-lawsuit-banner-trulaw

“The apparent decrease in mtDNA cleavage at higher drug concentrations is reminiscent of the effect of DNA intercalating anticancer drugs on nuclear topoisomerase II enzymes (29, 30). Intercalating anticancer drugs such as 2-methyl-9-hydroxyellipticinium and Adriamycin have been shown to stimulate topoisomerase II cleavage at low concentrations but inhibit cleavage at high drug concentrations.”

Fluoroquinolones are chemo drugs.  All topoisomerase interrupters are chemo drugs.  Don’t give people chemo drugs to treat sinus infections.  It’s not a difficult notion.

http://www.collective-evolution.com/2014/10/15/fda-allows-chemo-drugs-prescribed-antibiotics/

http://www.hormonesmatter.com/cipro-levaquin-avelox-fluoroquinolones-chemo-drugs/

“The non-exonuclease-treated DNA contained both linear and nicked circular forms of mtDNA but did not contain closed circular supercoiled mtDNA (Fig. 8, lane A), suggesting that ciprofloxacin induces single- as well as double stranded protein-linked breaks in the mtDNA.”

Thanks for breaking my DNA, Bayer.

“The current results indicate that ciprofloxacin is not cytotoxic unless cells are continuously exposed to drug for a minimum of three or four cell doublings. In comparison, drugs that target nuclear topoisomerase II trigger an apoptotic type of cell killing, even after a short 2-hr drug exposure.”

Interesting.  What is the time-frame for cell doubling?  And I don’t think that the question has been definitively answered as to whether or not fluoroquinolones are stored in lipids, continuously exposing cells to damage, or not.

“Another possibility is that the growth inhibitory and cytotoxic effects of ciprofloxacin are caused by the inhibition of an essential mitochondrial function or functions. This is supported by the following observations: First, treatment of mammalian cells with ciprofloxacin results in a selective depletion of mtDNA, leading to a decrease in mitochondrial respiration (6). These mitochondrial events precede the drug induced loss in cell growth and viability (Ref. 6 and current results). Second, cells become resistant to ciprofloxacin when they are grown under conditions that do not require mtDNA encoded functions. Third, ciprofloxacin induces the formation of site-specific, protein-linked breaks in mtDNA, indicating the presence of a drug-sensitive mitochondrial topoisomerase Il-like activity.”

Given the connections between ciprofloxacin and mitochondrial damage–depleting mtDNA and decreasing mitochondrial respiration, and the connections between mitochondrial damage and multiple chronic, multi-symptom illnesses, it is not absurd to make the assertion that ciprofloxacin, and other fluoroquinolones, can cause those diseases (autoimmune diseases, neurodegenerative diseases, fibromyaligia, autism, ME/Chronic Fatigue Syndrome, etc.).

The article, “Mitochondria Resuscitation: The Key to Healing Every Disease” by Chris D. Meletis, N.D. is a succinct and illustrative look at how mitochondria are related to multiple areas of health.

It’s nice and dandy that “cells become resistant to ciprofloxacin when they are grown under conditions that do not require mtDNA encoded functions” but human beings don’t have a bunch of cells that live in petri dishes that can grow without requiring our mitochondrial DNA functions.  I wonder what happens when human cells attempt to adapt to resist ciprofloxacin and adapt by ceasing to require mtDNA encoded functions.  I bet you a buck that no one knows the answer to that question.

Cipro breaks mitochondrial DNA.  WHY WASN’T THIS REPORT PAID ATTENTION TO?  All of the results in it warrant fluoroquinolones being taken off of the market until further investigation can be done.  This is absurd.  I know that there are cases where fluoroquinolones can save lives, I get that, and I’m usually decently reasonable about not calling for their removal from the market.  But this article spooked me severely.  We, collectively, have NO CLUE what the consequences of depleting our mitochondrial DNA are.

“Neither cell growth nor viability seems to be affected until cells have undergone three or four cell doublings in the presence of ciprofloxacin (Ref. 6 and current results). During this time span, the content of mtDNA decreases >90%, suggesting that drug is causing a loss in cell growth and viability by interfering with mtDNA replication.”

Nasty drugs – but if you metabolize them fast enough, they’re less nasty – apparently.

“Ciprofloxacin, as well as several other 4-quinolone drugs, can cause significant unwinding of DNA”

It’s what they’re designed to do.  They’re topoisomerase interrupters.  The mechanism of action for ciprofloxacin is, “The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.” (source)  It doesn’t take a rocket scientist to realize that drugs that inhibit the DNA and RNA replication, transcription, repair and recombination are dangerous.  I hate the FDA for allowing these dangerous drugs to be used as antibiotics.  It’s ludicrous.

Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in Ciprofloxacin-Treated Mammalian Cells” is not a hopeful article.  It is, frankly, a terrifying article.  More than 20 million prescriptions for fluoroquinolones are given out in Americans each year for the last couple decades, and that’s only a small portion of the prescriptions given worldwide.  What have we done to our collective mitochondrial DNA??  What are the consequences of depleting our mitochondrial DNA?  No one knows the answers to those questions.

Anyone who thinks that people aren’t sick with the diseases related to mitochondrial poisoning, isn’t looking very hard.  People are sick.  They’re in pain (peripheral neuropathy is thought to be caused by mitochondrial malfunctions), they’re depressed and suffering from even worse psychiatric disorders, they have heart conditions and metabolic disorders (source), ME/Chronic Fatigue Syndrome, autism, and many other misunderstood, chronic illnesses.  There are many potential culprits for the sorry state of human health in the 21st century, but fluoroquinolones aren’t even on the list according to most people.

FLUOROQUINOLONES DEPLETE MITOCHONDRIAL DNA, LEAD TO MITOCHONDRIAL DYSFUNCTION AND ALSO OBLITERATE THE MICROBIOME!

I’ll keep screaming it until I’m heard.

Back in 1992 it was noted that, “the interaction (of fluoroquinolones) with DNA is still of great concern because of the possible long-term genotoxicity of quinolone compounds, which are increasingly adopted as first-choice antibiotics for the treatment of many infections, and because it addresses the real mechanism of action of this class of molecules.”  (source)

I really wish that these warnings had been heeded.  Sadly, they’ve been ignored.

Our poor mitochondrial DNA.  I hope that mtDNA recovers and that the situation isn’t as dire as I suspect.  But the truth is, no one knows.  No one has a clue what the consequences of depleting mtDNA through unnecessary use of topoisomerase interrupting drugs are.

Floxies certainly know that the consequences of fluoroquinolones can involve a massive amount of pain and suffering.  It’s not okay.

Bayer, Johnson & Johnson, the FDA and everyone else involved with frivolously prescribing these drugs should be ashamed of themselves for failing to protect our mitochondrial DNA.  Topoisomerase interrupters should never have been approved for use as antibiotics.  It’s simply absurd.

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22 thoughts on “Study Finds that Ciprofloxacin Depletes Mitochondrial DNA

  1. Troy Fichter February 24, 2015 at 1:38 pm Reply

    Thanks Lisa!
    I see in the Article “Mitochondria Resuscitation” (the you referenced) that it suggest supplementing d-Ribose to help Mitochondria health and energy. Would this be related to “Cells deficient in mtDNA rely exclusively on glycolysis for energy.” Would appreciate you thoughts.

    Troy Fichter

    • Lisa Bloomquist February 24, 2015 at 8:28 pm Reply

      Hi Troy,

      Thanks for reading/commenting, and for checking out the “Mitochondrial Resuscitation” article, which I thought was quite well done. I honestly don’t know whether or not d-Ribose will help. I have read articles that praise both d-mannose and d-ribose, but I have also read articles that say that a ketogenic diet is good for mitochondria. Since d-mannose and d-ribose are sugars, I would think that those two things would be contradictory, but maybe there are some factors that make those things consistent that I’m not thinking of. I would think that d-ribose would be worth both looking into and trying. I don’t think it can hurt.

      Best regards,
      Lisa

  2. Greg Spooner February 24, 2015 at 7:24 pm Reply

    Great post (as usual… but this one really shines!). I’ve noticed that many athletic floxies are hit harder than some sedentary ones. I’m wondering if their higher metabolisms result in a shorter cell-doubling, causing them to accumulate more damage in a shorter time.

    • Lisa Bloomquist February 24, 2015 at 8:33 pm Reply

      Thanks, Greg! That’s a good point! Athletes also induce a lot of oxidative stress when they exercise, and since they’re already operating with a lot of oxidative stress, when they take a quin, it can just push them over the edge – I believe. But your point about metabolism is a good one too. Personally, I’ve always been fairly athletic and have had a decently fast metabolism. Maybe those were part of my personal risk factors that allowed me into club “floxie.” Who would have thought that being strong and having a fast metabolism could be curses? 😉

      Lisa

  3. fireflygbg February 25, 2015 at 3:28 pm Reply

    Here is that site!!!Read and listen to the audios all you can…and share!

    On Tue, Feb 24, 2015 at 1:19 PM, Floxie Hope wrote:

    > Lisa Bloomquist posted: ” This post contains quotes from the article > “Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in > Ciprofloxacin-Treated Mammalian Cells” that was published in Molecular > Pharmacology in 1996. It’s a good article. It’s an interesting and > damning a”

  4. Scott Rose February 25, 2015 at 10:19 pm Reply

    Hi Lisa,
    Researched Nutritionals makes a line of nutritional supplements that are supposedly designed to help repair damaged mitochondrial DNA: https://www.researchednutritionals.com/store/products.cfm?category=Mitochondria%2FATP&catid=22
    Do they work? I don’t know! I’d love to be optimistic about it and say PERHAPS! For me, their ATP FUEL product seems to have given me back some of the energy that I have lost since being floxed. I also take their RibosCardio product as well. I still have chronic fatigue, but it seems to have lessened a bit. Could be a placebo effect too, but I’m going to keep taking those products for now. I also take a ubiquinol product (UBQH from Integrative Nutritionals) as well.

    • Lisa Bloomquist February 26, 2015 at 4:22 pm Reply

      Cautiously optimistic is a good way to approach supplements, for sure! The mitochondrial support supplements have helped many people. Ruth describes her journey through FQ toxicity and how mito support supplements helped her well – https://floxiehope.com/ruths-story-cipro-toxicity/. I know that they haven’t helped everyone though. BUT, cautiously optimistic is still good and please let me know how you do!

      Regards,
      Lisa

  5. impossibleadversity March 9, 2015 at 2:13 pm Reply

    Great article again Lisa, I can’t comment much, except “pyrimidines, pyruvate, and elevated concentrations of glucose” is of interest. My own experience is that glucose/starch particularly with potassium helps with joint conditions over a few days. Also fatigue. From loose associations I figure uridine plays a part in all of these which is a pyrimidine.

  6. Vivi May 18, 2015 at 11:21 pm Reply

    Reblogged this on vitalkanal.

  7. Sasha July 22, 2015 at 4:37 pm Reply

    Did anyone try PQQ to increase the number of mitochondria? As increased mitochondria also means increased mitochondrial ROS I’d take it with MitoQ.

  8. […] Study Finds that Ciprofloxacin Depletes Mitochondrial DNA February 24, 2015 BY Floxie Hope by Lisa Bloomquist […]

  9. Carol Zwicker March 17, 2016 at 3:59 pm Reply

    What is PQQ?

  10. yeast display vector March 22, 2016 at 2:54 am Reply

    It’s always exciting to hear about new findings in DNA. Thanks for sharing!

  11. […] Fluoroquinolone antibiotics? “Very effective at killing bacteria! And mitochondria.” […]

  12. Bruce Niss July 30, 2016 at 3:38 pm Reply

    So if you have a HUGE mycoplasma infection (M. fermentans, hominis, arthritis, arthriditis, haemohominis, haemofelis, pneumonia….) and your immune system is so tanked that it gives no help when using mycoplsmastatic antibiotics, what’s a very sick, and chronic fatigued, guy supposed to do?

  13. Eric August 7, 2016 at 11:35 pm Reply

    It all becomes crystal clear when you understand the evolution of cell life on earth. All you have to do is appreciate one crucial reality: mitochondria ARE bacteria. They are prokaryotes: they are ancient bacteria that formed a symbiotic relationship with eukaryotic cells billions of years ago, co-evolving into the current modern eukaryote cell as we know it. Nonetheless they are still gram-negative bacteria still to this day. You cannot fool nature. Just because we don’t call mitochondria “bacteria,” or pretend it’s something different, nature is not fooled. Once one realizes this, and you put it together with the extraordinarily high, body-wide cell penetration capacity of the fluoroquinolone molecule, you understand how truly dangerous this drug is. Most especially when it enters a human cell with no bacterial pathogens present. The mitochondria become sitting ducks. This drug should never be used unless it is a life-threatening condition and the pathogen has been identified.

  14. Dr Edo McGowan October 2, 2016 at 3:32 pm Reply

    The push is to use recycled wasstewater (toilet to tap). The three FQs were detected in all the sewage samples tested in this work, with median concentrations between 34 and 251ng/L. What is the safe level for drinking water—Will the CDC, FDA and EPA be able to discuss this, ask them and get a rude awakening—–so, who deals with the Safe Drinking Water Act? in 2006 at the Environmental Law Conference in Yosemite, various papers were delivered. Session # 27 was to contain some interesting insight into this area of non-action by regulators. The topic was pharmaceuticals in groundwater. Of particular interest was the analysis of the SDWA by one of the US/EPA drinking water toxicologists. His delivered paper ended with the following: “Bottom line on almost all of the “emerging” contaminants that have attracted attention: It will be a long time, if ever, before they are regulated under the SDWA.”

  15. Jaci October 25, 2016 at 1:40 pm Reply

    And this latest post on Hormones Matter about Dr Naviaux’s metobolomics and the dauer state of the mitochondria is very encouraging. And also links to Dr Myhill talk very informative. The mitochondria doesn’t die, it goes into the dauer (sort of like hibernation, but not). I found all of it fascinating and hopeful

    http://www.healthrising.org/blog/2016/09/01/metabolomics-naviaux-chronic-fatigue-syndrome-core-problem/

    • Edo McGowan October 25, 2016 at 3:46 pm Reply

      Good, people are starting to pick up on these metabolic toxins coming through is water, so, imagine if you will that a banker making real estate loans, a politician in a city wanting a bigger tax base and some developers get together and decide to expand down around San Diego, because they can use the argument that there is abundant water because the big water agencies and the state have come up with a faux water called paper water. So building goes on for a couple of decades and there are a lot of new homes sold and everyone is happy. Then, the big water guys are taken to court and the fiction of paper water is exposed and the court says “there ain’t no such stuff” and poof, suddenly you built out based on fictional water but must supply something that is wet, so some other brilliant person says, I can save your ass—-there is toilet to tap but we will call it something nice like “water reuse.”

      So, now we have lots of politicians wanting in on this new miracle and lots of water industry, so it happens. One dirty hand washes the other and both come out clean. We hook up drinking water with sewage, but there are some minor flaws. Problem is that only scientists really looking at this know it has problems. Politicians really don’t care and the big water moguls need to watch the bottom line and cleaning up sewage, if done right, is hellishly expensive. So a lot of metabolic toxins get through, some with advance oxidation are converted into more toxic daughter byproducts and if taken in daily via water, do what to the metabolic motors, mitochondria and assembly on necessary metabolic machinery? But, we will use old standards and those old blind standards were never designed to do the presently needed job.

      Dr Edo McGowan

      ________________________________

  16. Foose December 29, 2016 at 7:19 pm Reply

    Thanks for this info. I’m a victim myself from recklessly prescribed antibiotics. Clindamycin hcl was one I was prescribe and I took another that I have know idea what they were. Now I have muscle pain in my legs with a buzzing affect, muscle twitching from head to toe, a sore throat for last 5 years, a swollen tougne, balance problems, slow wound healing and inability to loose weight. I’ve spent thousands of dollars trying supplements, and working with nature paths doctors, and yes it has helped a little but this article really puts it all together as to why I’m in the condition I’m in, and why I can’t get better
    Thank you for writing it.

  17. […] through which fluoroquinolones cause peripheral neuropathy. There is certainly evidence that fluoroquinolones damage mitochondria, and that damaged mitochondria are responsible for peripheral neuropathy. Given the evidence […]

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