El-Sayed El-Sayed M, Mansour Ahmed M, El-Sawy Waleed S
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21940. Epub 2017 Jun 9.
This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX-induced nephrotoxicity that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.
本研究旨在评估α-硫辛酸（ALA）对阿霉素（DOX）诱导的大鼠肾毒性的保护作用。单次静脉注射DOX（7.5mg/kg）可诱导肾毒性，表现为肾脏重量、肾/体重比、血清尿素、肌酐、肿瘤坏死因子α以及肾组织丙二醛、一氧化氮、环氧合酶-2和半胱天冬酶-3含量显著升高。此外，它还导致最终体重、血清白蛋白、肾组织还原型谷胱甘肽含量和超氧化物歧化酶活性显著降低。肾组织的组织病理学变化证实了肾毒性作用。相比之下，在DOX给药前14天及给药后7天口服ALA（50mg/kg）预处理可减轻肾毒性，表现为所检测的氧化应激、炎症和凋亡参数有更大改善。总之，ALA对DOX诱导的肾毒性具有显著的保护作用，这可能归因于其抗氧化、抗炎和抗凋亡活性。
