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对乙酰氨基酚诱导的小鼠肝损伤:某些药用植物对氧化防御系统的影响。

Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system.

作者信息

Olaleye M Tolulope, Rocha B T João

机构信息

Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Programa de pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Camobi, Cep 97105-900, Santa Maria, RS, Brazil.

出版信息

Exp Toxicol Pathol. 2008 Mar;59(5):319-27. doi: 10.1016/j.etp.2007.10.003. Epub 2007 Dec 3.

DOI:10.1016/j.etp.2007.10.003
PMID:18054472
Abstract

Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of hepatotoxicity of PCM. This work therefore seeks to induce liver damage in mice using single dose (25 0mg/kg) of acetaminophen and to evaluate the possible protective effects of administration (100mg/kg) of some medicinal plants (Kigelia africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) on PCM-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. Equally, comparative effects of these plants on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), gluthathione peroxidase (GPx), and delta-aminolevulinate dehydratase (delta-ALA-D) activities, were also evaluated in the mouse liver homogenate. Paracetamol caused liver damage as evident by statistically significant (P<0.05) increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, GPx, CAT, and delta-ALA-D and an increase in TBARS in the liver of paracetamol-treated group compared with the control group. However, all the tested plants except Calotropis procera were able to counteract these effects. The present results suggest that these plants can act as hepatoprotectives against paracetamol toxicity and that the mechanism by which they do this is by acting as antioxidants.

摘要

对乙酰氨基酚(扑热息痛,PCM)作为一种非处方镇痛药和解热药被广泛使用。大剂量摄入PCM可能导致严重的肝坏死。由PCM代谢物(N - 乙酰 - 对苯醌亚胺(NAPQI))的氧化能力介导的氧化应激被认为是PCM肝毒性的主要原因。因此,本研究旨在使用单剂量(250mg/kg)的对乙酰氨基酚诱导小鼠肝损伤,并评估给予一些药用植物(非洲吊灯树、牛角瓜、玫瑰茄和心叶山麻杆)(100mg/kg)对PCM诱导的小鼠肝损伤的可能保护作用。测定小鼠血浆中的丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性。同样,还在小鼠肝脏匀浆中评估了这些植物对脂质过氧化产物硫代巴比妥酸反应物质(TBARS)以及一些抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和δ-氨基乙酰丙酸脱水酶(δ-ALA-D)活性的比较影响。扑热息痛导致肝损伤,AST和ALT血浆活性的统计学显著升高(P<0.05)证明了这一点。与对照组相比,扑热息痛处理组小鼠肝脏中SOD、GPx、CAT和δ-ALA-D的活性普遍存在统计学显著下降,TBARS增加。然而,除牛角瓜外,所有测试植物都能够抵消这些影响。目前的结果表明,这些植物可以作为针对扑热息痛毒性的肝保护剂,并且它们这样做的机制是作为抗氧化剂发挥作用。

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