Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydrazine-induced colon carcinogenesis in a rat model. Male Wistar rats were divided into four groups and received high fat diet. Group 1 served as control, groups 2 and 4 were given a daily treatment of morin (50 mg/kg body weight) orally, everyday for a total period of 30 weeks. Groups 3 and 4 were given weekly subcutaneous injections of DMH at a dose of 20 mg/kg body weight in the groin for 15 weeks. Animals were sacrificed at the end of 30 weeks. The liver, intestine, colon and caecum from different groups were subjected to histopathological studies, determination of lipid peroxidation and antioxidant status. Our results showed decreased levels of liver enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation (LPO) products such as tissue thiobarbituricacid substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) in DMH treated rats, which were significantly (P < 0.05) reversed on morin supplementation. Moreover, intestinal, colonic and caecal TBARS, LOOH, CD and also the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and reduced glutathione (GSH) were significantly diminished in DMH treated rats, which were significantly (P < 0.05) elevated on simultaneous morin supplementation. Moreover, enhanced activity of intestinal, colonic and caecal ascorbic acid and alpha-tocopherol levels were also observed in DMH alone treated rats, which were significantly (P < 0.05) reduced on morin supplementation. These results indicate that morin could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

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1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

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