NSAIDs and FQs Damage Mitochondria, Increase Oxidative Stress, and Cause Cell Death

cell death

As I noted in the post, Why NSAIDs Suck for Floxies (and Probably Everyone Else Too), NSAIDs often exacerbate fluoroquinolone toxicity symptoms, and there are several mechanisms through which NSAIDs can interact with fluoroquinolones. The results of a recent article published in the Journal of Molecular and Cellular Cardiology by researchers at UC Davis, Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, help to further explain why NSAIDs trigger fluoroquinolone toxicity symptoms, and why they are a horrible combination.

NSAIDs and Fluoroquinolones Damage Mitochondria

The study showed that NSAIDs “Attack mitochondria, reducing the cardiac cell’s ability to produce energy” (source).

Likewise, fluoroquinolones have been shown to attack mitochondria. The studies, Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells and Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells show that fluoroquinolones damage mitochondria, deplete mitochondrial DNA, and cause oxidative stress.  Also, the FDA admits that mitochondrial damage is the likely mechanism through which fluoroquinolones cause peripheral neuropathy.

Healthy mitochondria are vital for cellular energy and health. Unhealthy mitochondria have been linked to many diseases, including M.S., fibromyalgia, M.E./C.F.S., P.O.T.S., diabetes, cancer, aging, and more. Do NSAIDs and fluoroquinolones increase one’s chances of getting those diseases that are related to mitochondrial dysfunction? It’s certainly reasonable to think so – via the mitochondrial damage link – but studies have not shown a direct connection (mainly because neither have been researched).

NSAIDs and Fluoroquinolones Increase Reactive Oxygen Species (ROS)

NSAIDs also “Cause the production of reactive oxygen species, which stresses heart cells and is associated with many diseases, including heart disease” (source).

Fluoroquinolones have also been shown to increase production of reactive oxygen species (ROS – aka oxidative stress). The article, Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients notes that, “Several in vitro and in vivo study using animals revealed that fluoroquinolones induced oxidative stress by producing reactive oxygen species (ROS)” and that in vivo human studies show that, “ciprofloxacin and levofloxacin induce more reactive oxygen species that lead to cell damage than gatifloxacin.

ROS are described as follows:

Without oxygen, we could not exist. However, in the process of generating energy by “burning” nutrients with oxygen, certain “rogue” oxygen molecules are created as inevitable byproducts. Known as free radicals and reactive oxygen species, these unstable, highly reactive molecules play a role in cell signaling and other beneficial processes when they exist in benign concentrations.  But when their numbers climb, as may occur as a result of aging and other conditions, they may wreak havoc with other molecules with which they come into contact, such as DNA, proteins, and lipids. As such, these “pro-oxidant” molecules become especially toxic.

In fact, a prevailing theory of disease and aging states that the gradual accumulation of pro-oxidant molecules, and the harm they incur, is responsible for many of the adverse changes that eventually cause various diseases. These include cancer (possibly triggered by free radical-induced damage to cellular DNA) and inflammatory and degenerative diseases such as Alzheimer’s, arthritis, atherosclerosis, and diabetes. While scientists have not yet reached consensus on the topic, accumulated evidence overwhelmingly identifies increased oxidative stress with age as a source of damage to cellular structure and function. (source)

To drastically over-simplify things, ROS are the opposite of antioxidants. If you’ve ever read about the benefits of antioxidants like vitamin C or glutathione, ROS have the opposite effects. In excess, ROS are harmful and damaging to cells.

NSAIDs and Fluoroquinolones Cause Cell Death

NSAIDs were found to “Impair the cardiac cell’s proteasome, the mechanism for degrading harmful proteins. This leads to toxic buildup and eventually to the death of cardiac cells” (source).

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Fluoroquinolones have also been found to cause cell death (apoptosis). This has been shown in many articles that note that fluoroquinolones are useful as chemotherapeutic agents specifically because they kill cells. Unfortunately, they don’t just kill cancer cells, they also kill healthy cells. The following articles note that fluoroquinolones are chemotherapeutic drugs that damage and kill cells:

  1. In an article published in the journal Urology, it was noted that, “Ciprofloxacin and ofloxacin exhibit significant time and dose-dependent cytotoxicity against transitional carcinoma cells.” That’s great – excellent, actually – if you happen to have carcinoma cells in your bladder. But if you just happen to have a bladder infection, chemo drugs that exhibit toxicity toward human cells – cancer or otherwise – are inappropriate for use (1).
  2. The mechanism for action for fluoroquinolones is that they are topoisomerase interrupters (2).Topoisomerases are enzymes that are necessary for DNA replication and reproduction. All of the other drugs that are topoisomerase interrupters are approved only for use as chemotherapeutic agents. It is only appropriate to use drugs that disrupt the process of DNA replication and reproduction when someone’s cells are already so messed up that they have cancer.
  3. Fluoroquinolones have been found to interfere with the DNA replication process for human mitochondria (3, 4, 5). Mitochondria are vital parts of our cells, (cellular energy is produced in our mitochondria), and disrupting the process through which mitochondrial DNA replicates causes cellular destruction, oxidative stress and disease.
  4. Fluoroquinolones have been shown to be genotoxic and to lead to chromosomal abnormalities in immune system cells (6).
  5. Fluoroquinolones disrupt cellular tubulin assembly (7). All of the other drugs that disrupt tubulin assembly are chemotherapeutic drugs.
  6. Fluoroquinolones disrupt enzymes, including CYP1A2 enzymes, which are necessary for detoxification.

Avoid NSAIDs and Fluoroquinolones

Dr. Aldrin V. Gomes, one of the authors of Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, “advised caution when using NSAIDs either topically or orally” (source). Likewise, caution is warranted when using fluoroquinolones, as one can gather from reading any of the stories of pain and suffering caused by fluoroquinolones. Personally, I will do everything in my power to avoid both NSAIDs and fluoroquinolones for the rest of my life. Mitochondrial destruction, oxidative stress, and cell death aren’t things I want.

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11 thoughts on “NSAIDs and FQs Damage Mitochondria, Increase Oxidative Stress, and Cause Cell Death

  1. cindy Meredith May 10, 2016 at 8:55 am Reply

    Thank you once again for an informative article about fluoroquinolones. As someone who was floxed but have mostly recovered (it’s been 8 months) from symptoms, can we expect that this cell damage can be reversed? It is very concerning. I looked back into my prescription history and found that I had taken levaquin and cipro at least 3 times in 9 months before the prescription that finally sent me over the edge.

  2. kris t May 10, 2016 at 9:03 am Reply

    Lisa, I can understand why taking both Cipro and Advil at the same time can be harmful, but what if you waited a year or two, after your body has healed, can you take Advil then? If I have a toothache, Tylenol just does not get rid of the pain like Advil. Are you saying that your Flox symptoms will return if you take NASIDS even years after taking your last Cipro or flouroquine drug? Kristin

    • Lisa May 10, 2016 at 9:25 am Reply

      Hi Kris,

      It seems to really depend on the person. For me, taking NSAIDs corresponded with my delayed FQ toxicity symptoms, so I’m going to avoid them from now on. Other people, for example Lizzy – https://floxiehope.com/lizzys-story-recovery-from-ciprofloxacin-poisoning-2/, are also set-back from taking a NSAID even long after they have finished taking FQs and all the FQs “should” be out of their system. Because of examples like those, I think that caution is warranted even long after the FQs should be out of your system. There are counter-examples too though, where people tolerate NSAIDs post-flox just fine. It truly seems to depend on the person. I very much think that caution should be used when taking NSAIDs though, as they do have side-effects and are bad for gut health and mitochondrial health.

      Have you tried kratom? Several floxies swear by it as an herbal painkiller.

      Have you seen a dentist about your toothaches? Maybe there’s something that a dentist can do to help too.

      Regards,
      Lisa

      • kris t May 10, 2016 at 9:50 am Reply

        Lisa, I think what you are saying has a lot of truth to it, because I took a half of a Celebrex on Friday for my arthritus, broke out in hives (probably because it contains sulfa which I am allergic to) and now this week, feel like I have the brain fog again. But not nearly as bad as when I first got off of Cipro last year. I was in a fog for months then. I think the tooth thing is sinus related. I may try taking a Sudafed for that. I heard kratom is addicitve and heard to get off of. I guess if I do try it, do I get it at a health food store?

        • Lisa May 10, 2016 at 10:00 am

          Kratom can be addictive, and caution should be exercised with use of it. I am not entirely sure how one manages that risk, but I made sure to only take it for acute pain episodes, not for chronic pain. I suggest asking people with more expertise than I have about the risk of addiction. There are kratom advocacy and information groups on facebook and other places online that may be helpful. When I was going through some pain, I got some kratom from a “head shop.” You can also get it online. I think it’s illegal in a couple of states (Indiana?), so check that before ordering it.

          Regards,
          Lisa

  3. Erika May 11, 2016 at 9:35 pm Reply

    Lisa, I am one of the ones that has been able to tolerate alleve after my antibiotic reaction. However, I only took it for 5 days when I was diagnosed with the tendosynovitis in my left forearm and wrist which I believe was a side effect of the cipro. That was at 8 months out. Since then, just this week (11 months out) I have had another flareup of the same thing and thanks to advice from other floxies on your site, I bathed my left hand, wrist, and forearm in epsom salt water. Symptoms and pain immediately disappeared with no recurrence yet. That sure beats taking alleve!!

  4. Ken January 13, 2017 at 4:09 am Reply

    I have tendinitis in my left foot tendons. I am also taking NSAIDS to reduce inflammation. How would I be able to tell if I can’t tolerate them?

    I have a hot feeling in my left calve and some hotness under the knee. I have noted some weakness in the leg and a lowering of strength. The tendons in my arms have started to ache a bit also, but I’ve been reading articles online nearly all day on my iPad, which tends to make my old somewhat recovered carpal tunnel flare up.

    I took 6 days of levofloxacin (Levaquin/Quixin). I felt a sharp pain in my foot on day 4. My doctor says I have not ruptured the tendon, but that I need proper ongoing rest.

    I am suffering from unusually high levels of anxiety and panic. The Internet doesn’t help. My limbs are heavy/tired at times.

    Question:
    How would I be able to tell if I can’t tolerate them?

    Does anyone have any stories about tendinitis they can share? Did it lead to rupture for some? (This is my biggest fear as my posterior tibiula is involved and that holds up my arch.)

    • kris t January 13, 2017 at 8:06 am Reply

      Ken, I was doubtful about the NSAIDs also. I am thinking what do these people know on this website, they are NOT doctors. So this past summer, i started up on them again, my pain is in my back and all my problems started again, the brain fog, the feeling that I was going crazy, awful, awful, went down to that dark place, anxiety a lot! I stopped taking the NSAIDS and within a few weeks, I started to feel better. I try not to use anything now, just ice. All the supplements recommended by either Lisa or Ruth did not help me and only made me feel worse. I did change my diet and ate only anti-biotic free meats. I guess my point here is that I agree with them now, its best to stay away from Advil and all that. Especially if it has not been that long since you stopped the anti-biotics. It will be two years this February when i stopped taking the Cipro. I would also suggest that you see a therapist, but you have to shop around to find the best one. Because some of them think you are downright crazy, but I found a good one and she helped a lot. Aquatics helped me also and I think that might help your legs. Chiropractic and massage did not help at all and in fact, made me worse. But everyone is different. Lisa always said that Time is the best thing and so you have to realize it just takes a lot of time to heal. Kris T

      • Ken January 16, 2017 at 3:16 am Reply

        Thank you, Kris.

        Did you recover okay from the initial pain caused by your back while using NSAIDs?

        I’m in pretty dire straights as far as options go. If I choose to not take them then the inflammation may not recede. The implications of that are lose of the arch in my left foot. I’m fighting tooth and nail to get that down because the financial burden is more than I can bare.

        Any other thoughts? Anyone not have issues with NSAIDs and was able to work through tendonitis?

        If I really have been effected by the levofloxacin and not just had it coming (or that the medication just worsened the situation) then I feel like it was one hell of an expensive UTI.

        • kris t January 16, 2017 at 7:23 am

          Ken, I still have the back pain so the NSAIDS did not help me. Can you use ice for your inflammation and Tylenol for the pain? Another idea would be to try the NSAID called Mobic as it is not as many milligrams as Advil, I think its only 15 and you can take one a day. Prescription only. I would go on Ruth’s story, here on this webpage and ask your tendonitius questions there as I think she had leg troubles and she can direct you on some ideas. Ruth has a continuous discussion going on her story site. Look on the column for Ruth’s story. Kris T

        • andshewasandstillis August 9, 2017 at 4:38 am

          An alternative to NSAIDs is Inflavonoid. It contains vit c and turmeric and was recommended by my chiropractor for pain and I flamation. I would check with your local alternative health person for your dosage. I was taking 2 three times a day to start and then 1 twice a day. Good luck

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