Hesperetin exerts dose dependent chemopreventive effect against 1,2-dimethyl hydrazine induced rat colon carcinogenesis.

Colon cancer is still one of the leading causes of death in USA and is increasing at an alarming rate in Asia. It is one of the major causes of death in industrialized countries, and its etiology is known to be a combination of hereditary, environmental, dietary factors and lack of physical activity. Chemoprevention plays a potential role in colorectal cancer. The present study was performed to evaluate the efficacy of hesperetin supplementation on colonic aberrant crypt foci, lipid peroxidation and antioxidant defense system in 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis in male Wistar rats. The rats were segregated into six groups viz., group 1, control rats received modified pellet diet; group 2 rats received modified pellet diet along with hesperetin (30 mg/kg body weight/day); groups 3-6 administrated DMH (20 mg/kg body weight) subcutaneous injection once a week for the first 4 weeks; in addition groups 4-6 received hesperetin at three different doses of 10, 20 and 30 mg/kg body weight/day for 16 weeks. All the rats were sacrificed at the end of the experimental period of 16 weeks. Increased tumor incidence and increased number aberrant crypt foci (ACF) accompanied by a decrease in the tissue lipid peroxidation, glutathione S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were observed in DMH-treated rats. Administration of hesperetin to DMH treated rats significantly decreased the tumor incidence, the number of aberrant crypt foci with simultaneous enhancement of tissue lipid peroxidation, GST, GPx, SOD, and CAT activities. The results of this study suggest that hesperetin at a dose of 20 mg/kg body weight showed a significant beneficial effect against chemically induced colonic carcinogenesis in rats as compared to the other two doses.

Aberrant crypt foci and AgNORs as putative biomarkers to evaluate the chemopreventive efficacy of pronyl-lysine in rat colon carcinogenesis.

Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-lysine, a key antioxidant present in bread crust by evaluating, the total number of aberrant crypt foci (ACF), their distributions, dysplastic ACF, colonic tumor incidence and the expression of cell proliferation biomarker such as the argyrophilic nucleolar organizing region-associated proteins (AgNORs) in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. Male Wistar rats were randomized into seven groups, group 1 were control rats, group 2 received pronyl-lysine (2 mg/kg body weight p.o. everyday), rats in groups 3-7 were administered DMH (20 mg/kg body weight) in the groin for 15 weeks. In addition, group 4 (pre-initiation), 5 (initiation), 6 (post-initiation), and 7 (entire period) received pronyl-lysine (2 mg/kg body weight p.o) everyday. At the end of 34 weeks, pronyl-lysine supplementation showed markedly reduced tumor incidence, ACF development and also lowered number of AgNORs. Overall, these findings confirm that pronyl-lysine has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.