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白藜芦醇对1,2-二甲基肼诱导的大鼠结肠癌发生过程中不同阶段结肠黏膜脂质过氧化、抗氧化状态及异常隐窝灶形成的调节作用

Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis.

作者信息

Sengottuvelan M, Senthilkumar R, Nalini N

机构信息

Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608 002, Tamilnadu, India.

出版信息

Biochim Biophys Acta. 2006 Aug;1760(8):1175-83. doi: 10.1016/j.bbagen.2006.03.008. Epub 2006 Apr 4.

DOI:10.1016/j.bbagen.2006.03.008
PMID:16733082
Abstract

To shed light on the association of lipid peroxidation and antioxidant status with the development of aberrant crypt foci (ACF), we studied the modulatory influence of resveratrol, supplemented in three dietary regimens (initiation, post-initiation and entire period) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were administered DMH (20 mg/kg body weight, s.c.) for 15 weeks and were supplemented with resveratrol (8 mg/kg body weight, p.o. everyday) in three dietary regimens. Intestines and colons were analyzed for the levels of diene conjugates (DC), lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS). Enzymic antioxidants (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; glutathione S-transferase, GST; and glutathione reductase, GR) and non-enzymic reserve (reduced glutathione, GSH; ascorbate; and alpha-tocopherol) were also assessed in the intestine and colon. Unsupplemented DMH exposed rats showed significantly decreased levels/activities of tissue DC, LOOHs, TBARS, SOD, CAT, GSH, GR and significantly elevated (P<0.05) GPX, GST, alpha-tocopherol and ascorbate as compared to control rats. Resveratrol supplementation during the entire period of the study resulted in significant (P<0.01) modulation of lipid peroxidation markers and antioxidants status, which were paralleled with ACF suppression, as compared to DMH-alone treated rats. These results indicate that resveratrol effectively inhibits DMH-induced ACF and colonic tumor development.

摘要

为了阐明脂质过氧化和抗氧化状态与异常隐窝灶(ACF)发生发展之间的关联,我们研究了白藜芦醇在三种饮食方案(启动期、启动后期和整个时期)中的调节作用,该物质对1,2 - 二甲基肼(DMH)诱导的结肠癌发生具有影响。给大鼠皮下注射DMH(20 mg/kg体重),持续15周,并在三种饮食方案中给予白藜芦醇(8 mg/kg体重,每天口服)。分析肠道和结肠中二烯共轭物(DC)、脂质氢过氧化物(LOOHs)和硫代巴比妥酸反应性物质(TBARS)的水平。还评估了肠道和结肠中的酶促抗氧化剂(超氧化物歧化酶,SOD;过氧化氢酶,CAT;谷胱甘肽过氧化物酶,GPX;谷胱甘肽S - 转移酶,GST;以及谷胱甘肽还原酶,GR)和非酶储备(还原型谷胱甘肽,GSH;抗坏血酸;以及α - 生育酚)。与对照大鼠相比,未补充白藜芦醇的DMH暴露大鼠的组织DC、LOOHs、TBARS、SOD、CAT、GSH、GR水平/活性显著降低,而GPX、GST、α - 生育酚和抗坏血酸显著升高(P<0.05)。与仅用DMH处理的大鼠相比,在整个研究期间补充白藜芦醇导致脂质过氧化标志物和抗氧化状态有显著(P<0.01)调节,这与ACF抑制平行。这些结果表明白藜芦醇有效抑制DMH诱导的ACF和结肠肿瘤发展。

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