Venkatachalam Karthikkumar, Gunasekaran Sivagami, Jesudoss Victor Antony Santiago, Namasivayam Nalini
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
Exp Toxicol Pathol. 2013 May;65(4):409-18. doi: 10.1016/j.etp.2011.12.005. Epub 2012 Jan 10.
This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kgb.w.). Groups 3-6 were induced colon cancer by injecting DMH (20 mg/kgb.w.) subcutaneously once a week for the first four weeks (groups 3-6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kgb.w. to groups 4-6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mgkg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kgb.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.
本研究旨在通过评估迷迭香酸(RA)对肿瘤形成、抗氧化酶、细胞色素P450含量、对硝基苯酚羟化酶和谷胱甘肽S-转移酶(GST)活性的影响,来研究其对1,2 - 二甲基肼(DMH)诱导的大鼠结肠癌发生的化学预防潜力。将大鼠分为六组,并在整个实验期间喂食改良颗粒饲料。第1组作为对照组,第2组接受RA(10毫克/千克体重)。第3 - 6组在前四周每周皮下注射一次DMH(20毫克/千克体重)以诱导结肠癌(第3 - 6组)。此外,分别给第4 - 6组大鼠按2.5、5和10毫克/千克体重的剂量给予RA。经DMH处理的大鼠出现大量结肠肿瘤;脂质过氧化减少;抗氧化状态降低;肝脏和结肠中细胞色素P450含量和对硝基苯酚羟化酶(PNPH)活性升高;GST活性降低。给经DMH处理的大鼠补充RA(5毫克/千克体重)可显著减少息肉数量(50%);逆转氧化应激标志物(21.0%)、抗氧化状态(38.55%)、细胞色素P450含量(29.41%)和PNPH活性(21.9%)。5毫克/千克体重剂量的RA显示出最显著的效果,可作为一种可能的结肠癌化学预防剂。