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脯氨酰赖氨酸对大鼠结肠癌发生过程中脂质过氧化和抗氧化状态的化学预防作用。

Chemopreventive efficacy of pronyl-lysine on lipid peroxidation and antioxidant status in rat colon carcinogenesis.

作者信息

Selvam Jayabal Panneer, Aranganathan Selvaraj, Gopalan Rama, Nalini Namasivayam

机构信息

Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.

出版信息

Fundam Clin Pharmacol. 2009 Jun;23(3):293-302. doi: 10.1111/j.1472-8206.2009.00670.x. Epub 2009 Mar 15.

Abstract

Colon cancer is a serious health problem in most of the countries and is the leading cause of cancer mortality throughout the world. The major objective of this study was to examine the chemopreventive effect of dietary pronyl-lysine (2 mg/kg body weight), a bread crust antioxidant, on intestinal and colonic tissue lipid peroxidation (LPO) and antioxidant status in rat colon carcinogenesis. Male Wistar rats were divided into seven groups and were fed a modified pellet diet for 34 weeks. Rats were given a weekly subcutaneous injection of 1,2-dimethyl hydrazine (DMH) (20 mg/kg body weight) for the first 15 weeks. Pronyl-lysine was supplemented to rats during the pre-initiation, initiation, post-initiation and also throughout the study period. All the rats were sacrificed at the end of 34 weeks and their colons were evaluated histologically. The activity of lipid peroxidation (LPO) and antioxidant status in the tissues such as the intestines, colon and cecum were estimated. Our results showed diminished levels of colonic, and cecal LPO products such as conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances, and also reduced activities of the antioxidants superoxide dismutase, catalase and glutathione dependent enzymes (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) in DMH-treated rats, while on supplementing dietary pronyl-lysine the levels of LPO products and antioxidants were significantly reversed (P < 0.05). Thus, our results strongly suggest that the administration of pronyl-lysine throughout the study period (group 7) and the post-initiation (group 6) stages of colon carcinogenesis significantly inhibits colon cancer incidence and prevents DMH induced histopathological lesions.

摘要

在大多数国家,结肠癌都是一个严重的健康问题,并且是全球癌症死亡的主要原因。本研究的主要目的是检验饮食中的戊糖赖氨酸(2毫克/千克体重)(一种面包皮抗氧化剂)对大鼠结肠癌发生过程中肠道和结肠组织脂质过氧化(LPO)及抗氧化状态的化学预防作用。将雄性Wistar大鼠分为七组,给予改良颗粒饲料喂养34周。在最初的15周内,每周给大鼠皮下注射1,2 - 二甲基肼(DMH)(20毫克/千克体重)。在起始前、起始、起始后以及整个研究期间都给大鼠补充戊糖赖氨酸。在34周结束时处死所有大鼠,并对其结肠进行组织学评估。估计肠道、结肠和盲肠等组织中的脂质过氧化(LPO)活性和抗氧化状态。我们的结果显示,在DMH处理的大鼠中,结肠和盲肠LPO产物(如共轭二烯、脂质氢过氧化物和硫代巴比妥酸反应性物质)的水平降低,抗氧化剂超氧化物歧化酶、过氧化氢酶和谷胱甘肽依赖性酶(谷胱甘肽过氧化物酶、谷胱甘肽 - S - 转移酶、谷胱甘肽还原酶)的活性也降低,而补充饮食中的戊糖赖氨酸后,LPO产物和抗氧化剂的水平显著逆转(P < 0.05)。因此,我们的结果强烈表明,在结肠癌发生的整个研究期间(第7组)和起始后(第6组)阶段给予戊糖赖氨酸可显著抑制结肠癌的发病率,并预防DMH诱导的组织病理学损伤。

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