Liu Hai-Xia, Li Jin, Li Qi-Xiong
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China.
Department of Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China.
Iran J Basic Med Sci. 2019 Mar;22(3):251-254. doi: 10.22038/ijbms.2019.32871.7851.
Doxorubicin (DXR)-induces glomerular atrophy and fibrosis in rat kidneys. The objective of the current study was to investigate the protective effects of valsartan on DXR-induced glomerular toxicity and its mechanisms of actions in rats.
Male Sprague-Dawley (SD) rats were divided into four groups, and each group contains ten rats. First group was control and was treated with saline only. Treatment groups were injected with DXR (6.5 mg/kg) alone, or intragastric gavage with 10 mg/kg or 20 mg/kg of valsartan after DXR treatment.
Rats treated with DXR only showed significant changes in concentrations of urinary protein, serum creatinine (SCr), and blood urea nitrogen (BUN). Moreover, glomerular structural damages were observed in rats treated with DXR. Valsartan significantly alleviated the effect of DXR. Dramatic elevation in malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) and significant reductions in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) were seen after DXR treatment. These effects were effectively ameliorated by co-administration with valsartan.
The findings of our study indicate that valsartan may play an important role in protecting DXR-induced renal toxicity, at least in part, through its antioxidant properties.
阿霉素（DXR）可导致大鼠肾脏肾小球萎缩和纤维化。本研究的目的是探讨缬沙坦对DXR诱导的大鼠肾小球毒性的保护作用及其作用机制。
雄性Sprague-Dawley（SD）大鼠分为四组，每组10只。第一组为对照组，仅用生理盐水治疗。治疗组分别单独注射DXR（6.5mg/kg），或在DXR治疗后用10mg/kg或20mg/kg缬沙坦进行灌胃。
仅用DXR治疗的大鼠尿蛋白、血清肌酐（SCr）和血尿素氮（BUN）浓度有显著变化。此外，在接受DXR治疗的大鼠中观察到肾小球结构损伤。缬沙坦显著减轻了DXR的作用。DXR治疗后丙二醛（MDA）、一氧化氮（NO）、一氧化氮合酶（NOS）显著升高，还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）水平显著降低。与缬沙坦联合使用可有效改善这些作用。
我们的研究结果表明，缬沙坦可能至少部分通过其抗氧化特性在保护DXR诱导的肾毒性中发挥重要作用。
