The following is a list of Medication-induced Mitochondrial Damage research studies:
1. Golomb, B. A., Koslik, H. J., & Redd, A. J. (2015). Fluoroquinolone-induced serious, persistent, multisymptom adverse effects. BMJ case reports, 2015, bcr2015209821. Abstract conclusion: We present a case series of four previously healthy, employed adults without significant prior medical history in each of whom symptoms developed while on fluoroquinolones (FQs), with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy, muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance. Physicians and patients should be alert to the potential for FQ-induced severe disabling multisymptom pathology that may persist and progress following FQ use. Known induction by FQs of delayed mitochondrial toxicity provides a compatible mechanism, with symptom profiles (and documented mechanisms of FQ toxicity) compatible with the hypothesis of an exposure-induced mitochondrial neurogastrointestinal encephalomyopathy.
2. Ghaly, H., Jörns, A., & Rustenbeck, I. (2014). Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells. European Journal of Pharmaceutical Sciences, 52, 206-214. Abstract conclusion: Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics, resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are due to stimulated insulin release by the inhibition of the KATP channel activity of the beta cell. Recently, it was found that fluoroquinolones were much less effective on metabolically intact beta cells than on open cell preparations. Thus the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial membrane potential, and the adenine nucleotide content of isolated pancreatic islets and beta cells. 100 μM of moxifloxacin abolished the NAD(P)H increase elicited by 20 mM glucose, while gatifloxacin diminished it and ciprofloxacin had no significant effect. This pattern was also seen with islets from SUR1 Ko mice, which have no functional KATP channels. Moxifloxacin also diminished the glucose-induced decrease of FAD-fluorescence, which reflects the intramitochondrial production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or gatifloxacin significantly reduced the effect of 20 mM glucose on the ATP/ADP ratio. The mitochondrial hyperpolarization caused by 20 mM glucose was partially antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin. Ultrastructural analyses after 20 h tissue culture showed that all three compounds (at 10 and 100 μM) diminished the number of insulin secretory granules and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced fission/fusion configurations of the beta cell mitochondria. In conclusion, fluoroquinolones affect the function of the mitochondria in pancreatic beta cells which may diminish the insulinotropic effect of KATP channel closure and contribute to the hyperglycaemic episodes.
3. Neustadt, J., & Pieczenik, S. R. (2008). Medication‐induced mitochondrial damage and disease. Molecular nutrition & food research, 52(7), 780-788. Abstract conclusion: Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others.
4. Kalghatgi, S., Spina, C. S., Costello, J. C., Liesa, M., Morones-Ramirez, J. R., Slomovic, S., ... & Collins, J. J. (2013). Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Science translational medicine, 5(192), 192ra85-192ra85. Abstract conclusion: Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.
5. Vichaya, E. G., Chiu, G. S., Krukowski, K., Lacourt, T. E., Kavelaars, A., Dantzer, R., ... & Walker, A. K. (2015). Mechanisms of chemotherapy-induced behavioral toxicities. Frontiers in neuroscience, 9. Abstract conclusion: A review of the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.
6. Labbe, G., Pessayre, D., & Fromenty, B. (2008). Drug‐induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundamental & clinical pharmacology, 22(4), 335-353. Abstract conclusion: Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects such as lactic acidosis and rhabdomyolysis in some patients. By severely altering mitochondrial function in the liver, drugs can induce microvesicular steatosis, a potentially severe lesion that can be associated with profound hypoglycaemia and encephalopathy. They can also trigger hepatic necrosis and/or apoptosis, causing cytolytic hepatitis, which can evolve into liver failure. Milder mitochondrial dysfunction, sometimes combined with an inhibition of triglyceride egress from the liver, can induce macrovacuolar steatosis, a benign lesion in the short term.
7. Brinkman, K., Smeitink, J. A., Romijn, J. A., & Reiss, P. (1999). Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. The Lancet, 354(9184), 1112-1115. Abstract conclusion: Highly active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome of peripheral fat wasting and central adiposity. HIV-1 protease inhibitors are generally believed to be the causal agents, although the syndrome has also been observed with protease-inhibitor-sparing regimens. Here, we postulate that the mitochondrial toxicity of the nucleoside-analogue reverse-transcriptase inhibitors plays an essential part in the development of this lipodystrophy, similar to the role of mitochondrial defects in the development of multiple symmetrical lipomatosis.
8. Chan, K., Truong, D., Shangari, N., & O'Brien, P. J. (2005). Drug-induced mitochondrial toxicity. Abstract conclusion: Disruption of mitochondrial function by drugs can result in cell death by necrosis or can signal cell death by apoptosis (e.g., following cytochrome c release). Drugs that injure mitochondria usually do so by inhibiting respiratory complexes of the electron chain; inhibiting or uncoupling oxidative phosphorylation; inducing mitochondrial oxidative stress; or inhibiting DNA replication, transcription or translation. It is important to test for mitochondrial toxicity early in drug development as impairment of mitochondrial function can induce various pathological conditions that are life threatening or can increase the progression of existing mitochondrial diseases.
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