Curcumin attenuates indomethacin-induced oxidative stress and mitochondrial dysfunction.
Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of indomethacin-induced enteropathy. We evaluated the potential of curcumin, a known cytoprotectant, as an agent to protect against such effects. Rats were pretreated with curcumin (40 mg/kg by intra-peritoneal injection) before administration of indomethacin (20 mg/kg by gavage). One hour later, the small intestine was isolated and used for assessment of parameters of oxidative stress. Mitochondria, brush border membranes (BBM) and surfactant-like particles (SLP) were also isolated from the tissue. Mitochondria were used for assessment of functional integrity, estimation of products of lipid peroxidation and lipid content. BBM were used for estimation of products of lipid peroxidation and lipid content, while the SLP were used for measurement of lipid content. The results showed that oxidative stress and mitochondrial dysfunction occurred in the small intestine of indomethacin-treated rats. Pre-treatment with curcumin was found to ameliorate these drug-induced changes. Significant changes were seen in some of the lipids in the mitochondria, BBM and SLP in response to indomethacin. However, curcumin did not have any significant effect on these drug-induced changes. We conclude that curcumin, by attenuating oxidative stress and mitochondrial dysfunction, holds promise as an agent that can potentially reduce NSAID-induced adverse effects in the small intestine.
Sivalingam
Nageswaran
N
Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil Nadu, India.
Basivireddy
Jayasree
J
Balasubramanian
Kunissery A
KA
Jacob
Molly
M
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003474:Curcumin / Q000494:pharmacology*; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013501:Surface-Active Agents; D000469:Alkaline Phosphatase; D003474:Curcumin; D007213:Indomethacin