Role of Grape Seed Extract on Methotrexate Induced Oxidative Stress in Rat Liver
Role of Grape Seed Extract on Methotrexate Induced Oxidative Stress in Rat Liver
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DOI：
10.1142/s0192415x08006302
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发表时间：
2008-01-01
影响因子：
5.7
通讯作者：
Sagdic, Osman
中科院分区：
文献类型：
--
作者：
Cetin, Aysun;Kaynar, Leylagul;Sagdic, Osman
甲氨蝶呤（MTX）是一种广泛使用的细胞毒性化疗药物，其作用机制往往因其严重的肝毒性而受到限制。关于影响。提出了几种假说，其中氧化应激是值得注意的。本文旨在探讨葡萄籽提取物（GSE）作为一种新型的天然自由基清除剂是否能改善mtx诱导的大鼠肝脏氧化损伤。这些动物被分成3组。每组12只。MTX-GSE组：大鼠口服GSE （100mg/kg体重）15 d，第10天再加单剂量MTX （20mg/kg，腹腔注射）。MTX组：这些患者接受安慰剂蒸馏水（口服）而不是GSE，持续15天，第10天同样的MTX方案应用于该组。对照组：连续15天给予蒸馏水（口服），第10天以生理盐水（腹腔）代替MTX。第16天，在深度麻醉下取肝组织标本。研究了组织匀浆中脂质过氧化终产物丙二醛（MDA）的水平以及两种重要的内源性抗氧化剂超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。MTX增加了肝脏匀浆中MDA水平，降低了SOD和CAT活性（p < 0.001），而GSE处理显著逆转了这些变化（p < 0.001）。MTX导致全血细胞计数参数显著降低（p < 0.05）。当补充GSE时，血液计数参数没有明显变化。GSE具有保护大鼠肝脏和抑制甲氨蝶呤诱导的氧化应激的作用。这些数据表明，GSE与甲氨蝶呤联合使用时可能具有治疗益处。
The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic the mechanisms of these adverse agent, is often limited by its severe hepatotoxicity. Regarding effects. several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether grape seed extract (GSE), a new natural free radical scavenger, Could ameliorate the MTX-induced oxidative injury in the rat liver. The animals were divided into 3 groups. Each group consisted of 12 animals. MTX-GSE group: rats were given GSE (100mg/kg body weight) orally for 15 days, and a single dose of MTX (20mg/kg, intraperitoneally) was added on the 10th day. MTX group: these received placebo distilled water (orally) instead of GSE for 15 days and the same MTX protocol applied to this group on the 10th day. Control group: rats were given distilled water (orally) through 15 days and physiological saline (intraperitoneally) instead of MTX was administered on the 10th day in a similar manner. On the 16th day, liver tissue samples were obtained under deep anaesthesia. The level of malondialdehyde (MDA), an end product of lipid peroxidation, and the activities of superoxide dismutase (SOD) and catalase (CAT), two important endogenous antioxidants, were evaluated in the tissue homogenates. MTX administration increased the MDA level and decreased the SOD and CAT activities in the liver homogenates (p < 0.001), while these alterations were significantly reversed by GSE treatment (p < 0.001). MTX led to significantly reduced whole blood count parameters (p < 0.05). When GSE was supplemented, no significant changes in blood Count parameters were noted. It appears that GSE protects the rat liver and inhibits methotrexate-induced oxidative stress. These data indicate that GSE may be of therapeutic benefit when used with MTX.