The modulatory influence of p-methoxycinnamic acid, an active rice bran phenolic acid, against 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant status and aberrant crypt foci in rat colon carcinogenesis.
We investigated the chemopreventive effect of p-methoxycinnamic acid (p-MCA), an active phenolic acid of rice bran, turmeric, and Kaemperfia galanga against 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 consisted of control rats that received a modified pellet diet and 0.1% carboxymethyl cellulose. The rats in Group 2 received a modified pellet diet supplemented with p-MCA [80 mg/kg body weight (b.wt.) post-orally (p.o.)] everyday. The rats in Groups 3-6 received 1,2-dimethylhydrazine (DMH) (20 mg/kg b.wt.) via subcutaneous injections once a week for the first 4 weeks; additionally, the rats in Groups 4, 5 and 6 received p-MCA at doses of 20, 40 and 80 mg/kg b.wt./day p.o., respectively, everyday for 16 weeks. The rats were sacrificed at the end of the experimental period of 16 weeks. The DMH-treated rats exhibited an increased incidence of aberrant crypt foci (ACF) development; an increased crypt multiplicity; decreased concentrations of tissue lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH); decreased levels of tissue enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR); and decreased levels of non-enzymic antioxidants such as reduced glutathione (GSH) and vitamins C, E and A in the colon. Supplementation with p-MCA significantly reversed these changes and significantly inhibited the formation of ACF and its multiplicity. Thus, our findings demonstrate that p-MCA exerts a strong chemopreventive activity against 1,2-dimethylhydrazine-induced colon carcinogenesis by virtue of its ability to prevent the alterations in DMH-induced circulatory and tissue oxidative stress and preneoplastic changes. p-MCA was more effective when administered at a dose of 40 mg/kg b.wt. than at the other two doses tested.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002 Tamilnadu, India.
Gunasekaran
G
Sivagami
Venkatachalam
V
Karthikkumar
Thangavel
T
Balasubramanian
Namashivayam
N
Nalini
D019813:1,2-Dimethylhydrazine; D058739:Aberrant Crypt Foci / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006651:Histocytochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002934:Cinnamates; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; C063318:4-methoxycinnamic acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D019813:1,2-Dimethylhydrazine