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.

Yiqi Fumai lyophilized injection attenuates doxorubicin-induced cardiotoxicity, hepatotoxicity and nephrotoxicity in rats by inhibition of oxidative stress, inflammation and apoptosis

“…54,58 By activating caspase-3 in renal proximal tubular cells and causing mitochondrial pathway, DOX probably leads apoptosis, which can arise renal cell damage and disorganized renal histology. 59 In present study, under the pretreatment of YQFM, expressions of BAX/Bcl-2 ratio, caspase-3 and cytochrome c were quite reduced, and then the inhibition of apoptosis could prevent tissue lesions and dysfunction, which was associated to the effect of ginsenosides included in YQFM. 38,60…”

3d metal complexes with meloxicam as therapeutic agents in the fight against human glioblastoma multiforme and cervical carcinoma

“…They also have, antioxidant effect, and free radical scavenging activity. [58] These findings further strengthen the interest to biological activity and The compounds were applied at a concentration of 500 mg/mL. DMSO-control cells were cultured in a medium containing 2% DMSO.…”

Protective effect of rutin on mercuric chloride‐induced reproductive damage in male rats

“…TNF‐α has importance in initiation and regulation of cytokine cascade in immune response process (Kuzu et al, ). Also, several studies have reported that COX‐2 increases TNF‐α production (Benzer et al, ; Caglayan, Temel, Kandemir, Yildirim, & Kucukler, ; Hassan, Ghobara, & Abd‐Allah, ). We found that rutin decreased TNF‐α and COX‐2 expression levels dose‐dependently.…”