An Yi, Xin Hui, Yan Wei, Zhou Xiaoxu
Department of Cardiology, The Affiliated Hospital of Qingdao University Medical College, China.
Exp Toxicol Pathol. 2011 Mar;63(3):215-9. doi: 10.1016/j.etp.2009.12.002. Epub 2010 Jan 8.
This study investigated the protective effects of pravastatin against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Pravastatin showed significant protection as evidenced by the decrease of elevated serum creatinine (CRE) and blood urea nitrogen (BUN), and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde (MDA) with a concomitant reduction of reduced glutathione (GSH) were inhibited by pravastatin, while the activities of kidney superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) were increased. The over expressions of kidney induced nitric oxide synthase (iNOS) and nitrotyrosine (3-NT) were suppressed by pravastatin. Pravastatin suppressed cisplatin-induced p38 mitogen-activated protein kinase (MAPK) activation in the kidney of mice. These results suggest that pravastatin pre-administration can prevent the nephrotoxicity induced by cisplatin. Pravastatin may exert the protective effect via inhibiting oxidative and nitrosative stress.
本研究探讨了普伐他汀对顺铂诱导的小鼠肾毒性的保护作用及其可能机制。普伐他汀表现出显著的保护作用，血清肌酐（CRE）和血尿素氮（BUN）升高降低以及顺铂诱导的组织病理学损伤改善可证明这一点。普伐他汀抑制了肾丙二醛（MDA）的形成并伴随还原型谷胱甘肽（GSH）的减少，同时增加了肾超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-px）的活性。普伐他汀抑制了肾诱导型一氧化氮合酶（iNOS）和硝基酪氨酸（3-NT）的过度表达。普伐他汀抑制了顺铂诱导的小鼠肾中p38丝裂原活化蛋白激酶（MAPK）的激活。这些结果表明，预先给予普伐他汀可预防顺铂诱导的肾毒性。普伐他汀可能通过抑制氧化应激和亚硝化应激发挥保护作用。
