Zhang Jiangong, Pan Xinjuan, Li Ning, Li Xing, Wang Yongchao, Liu Xiaozhuan, Yin Xinjuan, Yu Zengli
Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China ; Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Exp Ther Med. 2014 Jan;7(1):260-266. doi: 10.3892/etm.2013.1381. Epub 2013 Nov 5.
Oxidative stress is a recognized factor in nephrotoxicity induced by chronic exposure to inorganic arsenic (As). Grape seed extract (GSE) possesses antioxidant properties. The present study was designed to evaluate the beneficial effects of GSE against arsenic-induced renal injury. Healthy, male Sprague-Dawley rats were exposed to As in drinking water (30 ppm) with or without GSE (100 mg/kg) for 12 months. The serum proinflammatory cytokine levels and mRNA expression levels of fibrogenic markers in the renal tissues were evaluated using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The protein expression levels of nicotinamide adenine dinucleotide phosphate (NADPH) subunits, transforming growth factor-β1 (TGF-β1) and phosphorylated Smad2/3 (pSmad2/3) were assessed using western blot analysis. The results demonstrated that cotreatment with GSE significantly improved renal function, as demonstrated by the reductions in relative kidney weight (% of body weight) and blood urea nitrogen, and the increase in the creatinine clearance capacity. GSE attenuated the As-induced changes in the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β and the mRNA levels of TGF-β1, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) and fibronectin (FN) in renal tissue. Furthermore, administration of GSE markedly reduced As-stimulated reactive oxygen species (ROS) production and Nox activity, as well as the protein expression levels of the NADPH subunits (Nox2, p47phox and Nox4). In addition, GSE cotreatment was correlated with a significant reduction in TGF-β/Smad signaling, as demonstrated by the decreased protein levels of TGF-β1 and pSmad2/3 in renal tissue. This study indicated that GSE may be a useful agent for the prevention of nephrotoxicity induced by chronic exposure to As. GSE may exert its effects through the suppression of Nox and inhibition of TGF-β/Smad signaling activation.
氧化应激是长期接触无机砷（As）所致肾毒性的一个公认因素。葡萄籽提取物（GSE）具有抗氧化特性。本研究旨在评估GSE对砷诱导的肾损伤的有益作用。将健康雄性Sprague-Dawley大鼠暴露于含或不含GSE（100 mg/kg）的饮用水中的As（30 ppm）中12个月。分别使用酶联免疫吸附测定和定量聚合酶链反应评估血清促炎细胞因子水平和肾组织中纤维化标志物的mRNA表达水平。使用蛋白质印迹分析评估烟酰胺腺嘌呤二核苷酸磷酸（NADPH）亚基、转化生长因子-β1（TGF-β1）和磷酸化Smad2/3（pSmad2/3）的蛋白质表达水平。结果表明，与GSE联合治疗显著改善了肾功能，表现为相对肾重量（体重百分比）和血尿素氮降低，以及肌酐清除能力增加。GSE减轻了As诱导的肾组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β血清水平变化以及TGF-β1、α-平滑肌肌动蛋白（α-SMA）、结缔组织生长因子（CTGF）和纤连蛋白（FN）的mRNA水平变化。此外，给予GSE显著降低了As刺激的活性氧（ROS）产生和Nox活性，以及NADPH亚基（Nox2、p47phox和Nox4）的蛋白质表达水平。此外，如肾组织中TGF-β1和pSmad2/3蛋白质水平降低所示，GSE联合治疗与TGF-β/Smad信号传导的显著减少相关。本研究表明，GSE可能是预防长期接触As所致肾毒性的有用药物。GSE可能通过抑制Nox和抑制TGF-β/Smad信号传导激活发挥其作用。
