Hassan Memy H, Ghobara Mohamed, Abd-Allah Gamil M
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.
J Biochem Mol Toxicol. 2014 Aug;28(8):337-46. doi: 10.1002/jbt.21570. Epub 2014 May 3.
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.
阿霉素诱导的肾毒性掩盖了其抗癌效果。本研究旨在评估环氧化酶 -2 抑制剂美洛昔康对阿霉素诱导的小鼠肾毒性的可能调节作用，并探索一些调节机制。将 40 只雄性小鼠分为四组，分别用生理盐水、美洛昔康（每日）、阿霉素（每周两次）或美洛昔康与阿霉素联合处理 2 周。阿霉素导致肾脏相对体重与体重之比显著增加、肾脏脂质过氧化、白细胞介素 -6 和肿瘤坏死因子 -α 的血浆水平升高、肾脏半胱天冬酶 -3 活性增加以及肾脏前列腺素 E2（PGE2）含量增加。阿霉素扰乱了肾脏组织学，使肾功能测试（血清肌酐、尿酸和血尿素氮）结果异常，导致抗氧化酶活性（超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶）和还原型谷胱甘肽（GSH）含量显著降低。美洛昔康与阿霉素联合给药减轻了所有受阿霉素干扰的参数。美洛昔康通过抑制炎性 PGE2、炎性细胞因子、半胱天冬酶 -3 活性、抗氧化作用和自由基清除活性来改善阿霉素诱导的肾损伤。
