Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Pharmacol Rep. 2018 Aug;70(4):712-719. doi: 10.1016/j.pharep.2018.02.007. Epub 2018 Feb 5.
The aim of this study was to investigate the effect of ellagic acid (EA) on arsenic-induced renal and hepatic toxicity in rats.
A total number of 35 male Wistar rats were randomly divided into five experimental groups. Group 1 received normal saline (po). Group 2 received sodium arsenite (SA, 10mg/kg, po) for 21days. Group 3 received EA (30mg/kg, po) for 14days. Groups 4 and 5 received SA 7days prior to EA (10 and 30mg/kg respectively) treatment and continued up to 21days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were measured in kidney and liver.
Treatment with EA (more potently at dose of 30mg/kg) restored the SA-induced alterations in serum creatinine (Cr) and blood urine nitrogen (BUN) levels as well as the changes in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations (all p<0.001). Elevated levels of malondialdehyde (MDA) and nitric oxide (NO) in renal and hepatic tissue was reduced by EA treatment (all p<0.001). Treatment with EA enhanced the glutathione (GSH) content in liver (p<0.001) and up-regulated renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) mRNA expression (all p<0.001). The SA-induced histopathological alterations in kidney and liver were reduced by EA treatment.
In conclusion, the presence of EA with SA alleviated its toxic effects and EA treatment might be an effective strategy for the management of arsenic-induced renal and hepatic damage.
本研究旨在探讨鞣花酸（EA）对大鼠砷诱导的肾肝毒性的影响。
将 35 只雄性 Wistar 大鼠随机分为五组。第 1 组给予生理盐水（po）。第 2 组给予亚砷酸钠（SA，10mg/kg，po）21 天。第 3 组给予 EA（30mg/kg，po）14 天。第 4 组和第 5 组在给予 EA（分别为 10 和 30mg/kg）治疗前 7 天给予 SA，并与 SA 同时给予至 21 天。测量肾肝的各种生化、组织学和分子生物标志物。
EA（在 30mg/kg 剂量下更有效）治疗可恢复 SA 诱导的血清肌酐（Cr）和血液尿氮（BUN）水平改变以及天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）和丙氨酸氨基转移酶（ALT）浓度改变（均 p<0.001）。EA 治疗降低了肾肝组织中丙二醛（MDA）和一氧化氮（NO）的升高水平（均 p<0.001）。EA 治疗增加了肝组织中的谷胱甘肽（GSH）含量（p<0.001），并上调了肾肝超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）mRNA 表达（均 p<0.001）。EA 治疗减轻了 SA 诱导的肾肝组织学改变。
总之，EA 与 SA 共存可减轻其毒性作用，EA 治疗可能是管理砷诱导的肾肝损伤的有效策略。
