title: Modulator effects of meloxicam against doxorubicin-induced nephrotoxicity in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munaworah, P.O. Box 30001, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azahr University, Cairo, Egypt. memymahmoud@yahoo.com.
authors.forename: Memy H
authors.initials: MH
authors.lastname: Hassan
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ghobara
authors.forename: Gamil M
authors.initials: GM
authors.lastname: Abd-Allah
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D000077239:Meloxicam; D051379:Mice; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects*; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013843:Thiazines / Q000008:administration & dosage*; D013844:Thiazoles / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D013843:Thiazines; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D053148:Caspase 3; D015232:Dinoprostone; D000077239:Meloxicam
keywords: Cyclooxygenase-2; Cyclooxygenase-2 Inhibitors; Doxorubicin; Meloxicam