Modulatory efficacy of rosmarinic acid on premalignant lesions and antioxidant status in 1,2-dimethylhydrazine induced rat colon carcinogenesis

Abstract

Colorectal cancer is one of the leading causes of cancer related deaths in Western countries and is becoming increasingly common in Asia. Rosmarinic acid (RA), one of the major components of polyphenol possesses attractive remedial features. The purpose of this study is to investigate the possible chemopreventive mechanism of action of RA against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the circulatory antioxidant status and colonic bacterial enzymes activities. Additionally, we analyzed the aberrant crypt foci (ACF) formation and multiplicity in the colon of experimental groups. Wistar male rats were divided into six groups. Group 1 was control rats, group 2 rats received RA (10mg/kg b.w., p.o. everyday), rats in groups 3–6 received DMH (20mg/kg b.w., s.c.) for the first 4 weeks. In addition to DMH, groups 4–6 received 2.5, 5, and 10mg/kg b.w. RA respectively. The results revealed that supplementation with RA significantly reduced the formation of ACF and ACF multiplicity in DMH treated rats. Moreover RA supplementation prevented the alterations in circulatory antioxidant enzymes and colonic bacterial enzymes activities. Overall, our results showed that all three doses of RA inhibited carcinogenesis, though the effect of the intermediary dose of 5mg/kg b.w. was more pronounced.