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

Jayabal Panneer Selvam, Selvaraj Aranganathan, Rama Gopalan, Namasivayam Nalini
Fundamental & Clinical Pharmacology 2009, 23 (3): 293-302
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.

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