Protective activity of gallic acid against glyoxal -induced renal fibrosis in experimental rats.
Protective activity of gallic acid against glyoxal -induced renal fibrosis in experimental rats.
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DOI：
10.1016/j.toxrep.2015.07.007
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发表时间：
2015
影响因子：
--
通讯作者：
Vellaichamy E
中科院分区：
文献类型：
--
作者：
Yousuf MJ;Vellaichamy E
本研究旨在评估没食子酸（GA）对乙二醛（GO）（一种晚期糖基化中间体诱导的实验大鼠肾纤维化）的保护活性。乙二醛（腹腔注射）剂量为 15 毫克/公斤体重/天，持续 4 周，可诱导肾纤维化。 GA 与 GO 一起口服给药（100 毫克/公斤体重/天），持续 4 周。分别使用 mRNA 表达分析和 Masson 三色染色 (MTS) 测量肾组织中胶原蛋白的合成和沉积，分析 GA 的抗纤维化活性。 GA 的肾保护潜力通过量化肾脏损伤标志物（如血清血尿素氮 (BUN)、肌酐 (CR) 和碱性磷酸酶 (AP)）来评估。此外，通过高碘酸希夫（PAS）染色分析肾组织的基底膜损伤。与单独输注 GO 的大鼠相比，GA 联合治疗显着抑制了 GO 诱导的胶原蛋白 I 和 III、MMP-2、MMP-9 和 NOX（分别为 p < 0.05）基因 mRNA 表达的升高。此外，GA 联合治疗显着减弱了 GO 诱导的血清标记物（如 BUN、CR 和 AP 水平）的升高（分别为 p < 0.05）。此外，GA 联合治疗恢复了降低的肾脏超氧化物歧化酶 (SOD) 活性 (p < 0.05)，从而减轻了活性氧 (ROS) 的产生，并维持了肾小球的正常结构。本研究清楚地表明，GO 通过增强 GO/晚期糖基化终产物受体 (RAGE) 诱导的 ROS 生成来诱导肾纤维化，而 GA 通过其 ROS 猝灭和抗糖化活性有效地抵消了 GO 诱导的肾纤维化。
This study was designed to evaluate the protective activity of gallic acid (GA) against glyoxal (GO) an advanced glycation intermediate-induced renal fibrosis in experimental rats. Glyoxal (i.p) at a dose of 15 mg/Kg body weight/day for 4 weeks induces renal fibrosis. GA was administered orally (100 mg/Kg body weight/day) along with GO for 4 weeks. The anti-fibrotic activity of GA was analyzed by measuring the collagen synthesis and deposition in renal tissues using mRNA expression analysis and Masson trichrome staining (MTS), respectively. The nephroprotective potential of GA was assessed by quantifying the markers of kidney damage such as serum blood-urea-nitrogen (BUN), creatinine (CR) and alkaline phosphatase (AP). Moreover, basement membrane damage in renal tissues was analysed by periodic acid Schiff’s (PAS) staining. GA co-treatment markedly suppressed the GO-induced elevation in mRNA expression of collagenIand III, MMP-2, MMP-9 and NOX (p < 0.05, respectively) genes as compared with GO alone infused rats. In addition, GA co-treatment significantly attenuated the GO -induced elevation in serum markers such as BUN, CR and AP levels (p < 0.05, respectively). Furthermore, GA co-treatment restored back the decreased renal super oxide dismutase (SOD) activity (p < 0.05) thereby assuage the reactive oxygen species (ROS) generation, and maintained the normal architecture of glomerulus. The present study clearly indicates that GO -induces renal fibrosis by enhancing GO/receptor of advanced glycation end product (RAGE) induced ROS generation and GA effectively counteracted GO-induced renal fibrosis by its ROS quenching and anti-glycation activity.