Modulator Effects of Meloxicam against Doxorubicin‐Induced Nephrotoxicity in Mice

Doxorubicin‐induced renal toxicity overshadows its anticancer effectiveness. This study is aimed at assessing the possible modulator effects of meloxicam, a cyclooxigenase‐2 inhibitor, on doxorubicin‐induced nephrotoxicity in mice and exploring some of the modulator mechanisms. Forty male mice were divided for treatment, for 2 weeks, with saline, meloxicam (daily), doxorubicin (twice/week), or both meloxicam and doxorubicin. Doxorubicin induced a significant increase in relative kidney weight to body weight, kidney lipid perooxidation, plasma levels of interleukin‐6 and tumor necrosis factor‐α, kidney caspase‐3 activity, and kidney prostaglandin E2 (PGE2) content. Doxorubicin disturbed kidney histology, abrogated renal function tests (serum creatinine, uric acid, and blood urea nitrogen), induced a significant decrease in antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and catalase) and reduced glutathione (GSH) content. The administration of meloxicam with doxorubicin mitigated all doxorubicin‐disturbed parameters. Meloxicam ameliorated doxorubicin‐induced renal injury via inhibition of inflammatory PGE2, inflammatory cytokines, caspase‐3 activity, antioxidant effect, and free radical scavenging activity.