Zinc prevents indomethacin-induced renal damage in rats by ameliorating oxidative stress and mitochondrial dysfunction.
The clinical utility of non-steroidal anti-inflammatory drugs (NSAIDs) is limited by their gastrointestinal and renal toxicities. Indomethacin (an NSAID commonly used in toxicity studies) has been shown to induce significant oxidative stress and mitochondrial dysfunction in the rat kidney. The current study was designed to assess the potential of zinc, a known antioxidant, to protect the kidney against these drug-induced effects. Male Wistar rats were pre-treated with zinc sulphate (50 mg/kg) and dosed with indomethacin (20 mg/kg) by oral gavage. Rats were sacrificed 24 h after the dose of indomethacin. Parameters of oxidative stress, mitochondrial function and lipid content of the mitochondrial membranes were measured in the kidneys of these animals. It was found that zinc significantly attenuated indomethacin-induced oxidative stress, mitochondrial dysfunction and changes in the lipids in mitochondrial membranes in the kidney. The content of metallothionein, a cysteine-rich zinc-binding protein, was also determined in the tissue. There was no significant induction of metallothionein in the kidney in zinc-treated animals. Estimation of serum creatinine showed that zinc seemed to hasten functional recovery of the kidney following indomethacin administration. We conclude that pretreatment with zinc is effective in protecting against indomethacin-induced changes in the rat kidney. This protective effect does not appear to be mediated by metallothionein.
Varghese
Joe
J
Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil Nadu, India. joevarghese@cmcvellore.ac.in
Faith
Minnie
M
Jacob
Molly
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000975:Antioxidants / Q000494:pharmacology*; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004798:Enzymes; D017382:Reactive Oxygen Species; D015032:Zinc; D007213:Indomethacin