In this regard, the present review provides a comprehensive insight of the existing knowledge and recent developments on NSAID-induced organ damage. Although extensive research has elucidated the mechanisms underlying the clinical hazards of NSAIDs, no review has extensively collated the outcomes on various multiorgan toxicities of these drugs together. However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Owing to the efficacy in reducing pain and inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines confirming their position in the WHO’s Model List of Essential Medicines. , Superoxide CVD, Cardiovascular disease TNF-α, Tumor necrosis factor-alpha NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells ICAM-1, Intercellular adhesion molecule 1 MAPK, Mitogen activated protein kinase PKC, Protein kinase C DRP1, Dynamin-related protein 1 LPS, Lipopolysaccharide HMGB1, High mobility group box 1 DAMP, Damage associated molecular pattern MEDAL, Multinational Etoricoxib and Diclofenac Arthritis Long-term trial GI, Gastrointestinal MI, Myocardial infarction HF, Heart failure VIGOR, Vioxx Gastrointestinal Outcomes Research APPROVe, Adenomatous Polyp PRevention On Vioxx trial PRECISION, Prospective Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen NANSAIDs, Non aspirin NSAIDs ADMA, Asymmetric dimethyl arginine eNOS, Endothelial nitric oxide synthase CKD, Chronic kidney disease AKI, Acute kidney injury GFR, Glomerular filtration rate PPAR, Peroxisome proliferator-activated receptor CRESCENT, Celecoxib Rofecoxib Efficiency and Safety in Cormorbidities Evaluation Trial ICH, Intracerebral haemorrhage AERD, Aspirin-exacerbated respiratory disease CAP, Community Acquired Pneumonia Cys-LTEs, Cysteinyl leukotrienes Abbreviations: NSAID, Non-steroidal anti-inflammatory drug PGHS, Prostaglandin-endoperoxide synthase PG, Prostaglandin FDA, US Food and Drug Administration IC, Inhibitory concentration P450, Cytochromes P450 PLA, Phospholipase Tx, Thromboxane LTE, Leukotriene MOS, Mitochondrial oxidative stress ETC, Electron transport chain O 2.
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