Induction of mitochondrial toxicity by non-steroidal anti-inflammatory drugs (NSAIDs): The ultimate trade-off governing the therapeutic merits and demerits of these wonder drugs.

Autor: Mazumder S; Department of Zoology, Raja Peary Mohan College, 1 Acharya Dhruba Pal Road, Uttarpara, West Bengal 712258, India., Bindu S; Department of Zoology, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal 736101, India., Debsharma S; Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, West Bengal, India., Bandyopadhyay U; Department of Biological Sciences, Bose Institute, Unified Academic Campus, EN 80, Sector V, Bidhan Nagar, Kolkata 700091, West Bengal, India. Electronic address: udayb@jcbose.ac.in.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Oct; Vol. 228, pp. 116283. Date of Electronic Publication: 2024 May 13.
DOI: 10.1016/j.bcp.2024.116283
Abstrakt: Non-steroidal anti-inflammatory drugs (NSAIDs) are most extensively used over-the-counter FDA-approved analgesic medicines for treating inflammation, musculoskeletal pain, arthritis, pyrexia and menstrual cramps. Moreover, aspirin is widely used against cardiovascular complications. Owing to their non-addictive nature, NSAIDs are also commissioned as safer opioid-sparing alternatives in acute trauma and post-surgical treatments. In fact, therapeutic spectrum of NSAIDs is expanding. These "wonder-drugs" are now repurposed against lung diseases, diabetes, neurodegenerative disorders, fungal infections and most notably cancer, due to their efficacy against chemoresistance, radio-resistance and cancer stem cells. However, prolonged NSAID treatment accompany several adverse effects. Mechanistically, apart from cyclooxygenase inhibition, NSAIDs directly target mitochondria to induce cell death. Interestingly, there are also incidences of dose-dependent effects where NSAIDs are found to improve mitochondrial health thereby suggesting plausible mitohormesis. While mitochondria-targeted effects of NSAIDs are discretely studied, a comprehensive account emphasizing the multiple dimensions in which NSAIDs affect mitochondrial structure-function integrity, leading to cell death, is lacking. This review discusses the current understanding of NSAID-mitochondria interactions in the pathophysiological background. This is essential for assessing the risk-benefit trade-offs of NSAIDs for judiciously strategizing NSAID-based approaches to manage pain and inflammation as well as formulating effective anti-cancer strategies. We also discuss recent developments constituting selective mitochondria-targeted NSAIDs including theranostics, mitocans, chimeric small molecules, prodrugs and nanomedicines that rationally optimize safer application of NSAIDs. Thus, we present a comprehensive understanding of therapeutic merits and demerits of NSAIDs with mitochondria at its cross roads. This would help in NSAID-based disease management research and drug development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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