Modulating effect of d-carvone on 1,2-dimethylhydrazine-induced pre-neoplastic lesions, oxidative stress and biotransforming enzymes, in an experimental model of rat colon carcinogenesis.

OBJECTIVE

The present study has aimed to evaluate chemopreventive potential of d-carvone on oxidative stress markers, biotransforming enzymes, incidence of colonic polyps and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis.

METHODS

Rats were randomly divided into six groups, with group I serving as control. Group II animals received d-carvone every day orally (20 mg/kg body weight) for 16 weeks; groups III-VI received subcutaneous injections of DMH (20 mg/kg body weight) once a week, for the first 4 weeks. In addition, groups IV-VI received different doses of d-carvone (5, 10 and 20 mg/kg body weight everyday orally) along with DMH injections.

RESULTS

Our results revealed that supplementation with d-carvone significantly reduced incidence of polyps/ACF and ACF multiplicity in DMH-exposed rats compared to DMH-alone-exposed rats. Moreover, our results showed reduced activities of liver and circulatory antioxidants and increased levels of lipid peroxidation by products in DMH-exposed animals, which were significantly reversed on supplementation with d-carvone. In addition, colonic antioxidants and lipid peroxidation were significantly diminished in DMH-exposed rats, which were significantly elevated on supplementation with d-carvone. Furthermore, we also determined activities of biotransforming enzymes, which were found to be altered in DMH-exposed rats, but reversed on d-carvone supplementation. All these observations of changes were supported by histochemical findings.

CONCLUSIONS

Overall, results obtained from this study suggest that d-carvone at 10 mg/kg body weight provided optimum protection and could be used as an effective chemopreventive agent against colon carcinogenesis induced by DMH.