Modulator Effects of Meloxicam against Doxorubicin-Induced Nephrotoxicity in Mice
Version of Record online: 3 MAY 2014
© 2014 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 28, Issue 8, pages 337–346, August 2014
How to Cite
Hassan, M. H., Ghobara, M. and Abd-Allah, G. M. (2014), Modulator Effects of Meloxicam against Doxorubicin-Induced Nephrotoxicity in Mice. J. Biochem. Mol. Toxicol., 28: 337–346. doi: 10.1002/jbt.21570
- Issue online: 4 AUG 2014
- Version of Record online: 3 MAY 2014
- Manuscript Accepted: 7 APR 2014
- Manuscript Revised: 4 APR 2014
- Manuscript Received: 22 FEB 2014
- Cyclooxygenase-2 Inhibitors;
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.