Indomethacin-induced renal damage: role of oxygen free radicals

Basivireddy, Jayasree ; Jacob, Molly ; Pulimood, Anna B. ; Balasubramanian, Kunissery A. (2004) Indomethacin-induced renal damage: role of oxygen free radicals Biochemical Pharmacology, 67 (3). pp. 587-599. ISSN 0006-2952

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Nonsteroidal anti-inflammatory drugs are used extensively in clinical medicine. In spite of their therapeutic utility, however, they are known to cause significant gastrointestinal and renal toxicities, circumstances that limit their use. The side effects produced in these organs have been attributed mainly to the inhibitory effect of these drugs on the activity of cyclooxygenase, a key enzyme in prostaglandin synthesis. In addition to this, in the small intestine it is known that reactive oxygen species also contribute to the enteropathy seen in response to these drugs. In the kidney, however, there is little information whether other mechanisms contribute to the renal toxicity. This study was designed to look at the possible biochemical mechanisms involved in indomethacin-induced renal damage. Rats fasted overnight were dosed with indomethacin (20 mg/kg) by gavage and sacrificed 24 hr later. Histology of the kidney showed abnormalities in the mitochondria in the proximal tubules. Evidence of oxidative stress was found in the kidney associated with mitochondrial dysfunction and neutrophil infiltration. The lipid composition in the mitochondria was also altered. Such effects were abolished by the prior administration of arginine, a donor of nitric oxide. This study, thus, suggests that one of the mechanisms by which nonsteroidal anti-inflammatory drugs induce renal damage is through oxygen free radicals possibly generated by activated neutrophils and mitochondrial dysfunction.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Kidney; Indomethacin; Nitric Oxide; Nonsteroidal Anti-inflammatory Drugs; Oxidative Stress
ID Code:1474
Deposited On:05 Oct 2010 12:27
Last Modified:13 May 2011 06:02

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