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Induction of Nephrotic Syndrome in Mice by Retrobulbar Injection of Doxorubicin and Prevention of Volume Retention by Sustained Release Aprotinin
Published on: May 6, 2018
Modulator effects of meloxicam against doxorubicin-induced nephrotoxicity in mice
Memy H Hassan1, Mohamed Ghobara, Gamil M Abd-Allah
1Department 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.
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.
Insights
Meloxicam, a cyclooxygenase-2 inhibitor, mitigates doxorubicin-induced kidney damage in mice. It reduces inflammation, oxidative stress, and improves kidney function, offering a potential protective strategy against chemotherapy side effects.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Doxorubicin is a potent anticancer drug but causes significant kidney toxicity.
- Cyclooxygenase-2 (COX-2) inhibitors like meloxicam may offer protective effects against drug-induced organ damage.
Purpose of the Study:
- To evaluate meloxicam's protective effects against doxorubicin-induced nephrotoxicity in mice.
- To investigate the underlying mechanisms of meloxicam's modulatory action.
Main Methods:
- Male mice were treated with saline, meloxicam, doxorubicin, or a combination of meloxicam and doxorubicin for two weeks.
- Kidney function, oxidative stress markers, inflammatory cytokines, and histological changes were assessed.
Main Results:
- Doxorubicin significantly increased kidney weight, lipid peroxidation, inflammatory markers (IL-6, TNF-α, PGE2), and caspase-3 activity.
- Doxorubicin impaired renal function, reduced antioxidant enzyme activity (SOD, GPx, CAT), and depleted glutathione (GSH).
- Meloxicam co-administration counteracted all doxorubicin-induced detrimental effects, preserving kidney function and histology.
Conclusions:
- Meloxicam effectively ameliorates doxorubicin-induced nephrotoxicity in mice.
- The protective mechanisms involve inhibition of PGE2, inflammatory cytokines, caspase-3 activity, and antioxidant/free radical scavenging effects.
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