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Inhibitory effect of bread crust antioxidant pronyl-lysine on two different categories of colonic premalignant lesions induced by 1,2-dimethylhydrazine

Panneerselvam, Jayabal; Aranganathan, Selvaraj; Nalini, Namasivayam

European Journal of Cancer Prevention: August 2009 - Volume 18 - Issue 4 - p 291-302
doi: 10.1097/CEJ.0b013e32832945a6
Research papers: Colon Cancer

Colorectal malignancies continue to be one of the most frequent and life-threatening diseases throughout the world. Pronyl-lysine, a product obtained from bread crust, is a potent free radical scavenging antioxidant exerting chemopreventive activity by reducing oxidative stress. This study was conducted to investigate the effects of pronyl-lysine supplementation on the formation of colonic precancerous lesions, circulatory lipid peroxidation, and enzymic antioxidant status in 1,2-dimethylhydrazine-induced colon carcinogenesis. Male Wistar rats were randomized into seven groups; group 1 was control rats, group 2 received pronyl-lysine (2 mg/kg body weight orally) everyday, rats in groups 3–7 were administered subcutaneous 1,2-dimethylhydrazine (20 mg/kg body weight) once a week for 15 consecutive weeks. In addition, group 4 (pre-initiation), 5 (initiation), 6 (post-initiation), and 7 (entire period) received pronyl-lysine (2 mg/kg body weight orally) everyday. At the end of 34 weeks, indicative markers of lipid peroxidation and changes in antioxidant defense system were measured in circulation. The results showed that 1,2-dimethylhydrazine significantly increased total aberrant crypt foci formation, total number of dysplastic foci, β-catenin accumulated crypts and proliferating cell nuclear antigen labeling index in the colon, and enhanced lipid peroxidation markers and decreased enzymic antioxidant activities in the plasma and erythrocyte lysate as compared with untreated controls. Pronyl-lysine supplementation significantly reversed the changes as compared with the rats treated with 1,2-dimethylhydrazine alone. The effect of pronyl-lysine was more pronounced when supplemented throughout the study period (group 7). These findings suggest that pronyl-lysine suppresses 1,2-dimethylhydrazine-induced colon carcinogenesis effectively.

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

Correspondence to Professor Namasivayam Nalini, Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608 002, Tamilnadu, India

Tel: +91 4144 238343; fax: +91 4144 239141;


Received 2 December 2008 Accepted 30 December 2008

© 2009 Lippincott Williams & Wilkins, Inc.