Coenzyme Q10 attenuated DMH-induced precancerous lesions in SD rats.
Coenzyme Q10 (CoQ10) is known to be a compound with mitochondrial bioenergetic functions and antioxidant activity. In this study, we evaluated the effect of CoQ10 on the formation of aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH), DMH-induced leukocytic DNA damage and gene expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by real-time PCR in colonic mucosa of male SD rats. The animals were divided into three groups and fed a casein-based high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) with or without CoQ10 (0.4 mg in soybean oil/kg BW/d, i.p.). One week after beginning the diets, the rats were subjected to 6 wk of treatment with DMH (30 mg/kg/wk, s.c.) and CoQ10 treatments continued over the entirety of the experimental period (59 d). Administration of CoQ10 resulted in reduction of ACF numbers, to 20% of the carcinogen control value. CoQ10 supplementation induced an antigenotoxic effect on DMH-induced DNA damage in the blood cells. Colonic mucosa of DMH-injected rats had significantly greater COX-2 and iNOS gene expression than those of control rats, while treatment with CoQ10 induced an inhibitory effect on over-expression of COX-2 and iNOS in colon tumors. Our results provide evidence that CoQ10 has a protective effect on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, possibly by modulating COX-2 and iNOS gene expression in colonic mucosa and DNA damage in leukocytes, suggesting that CoQ10 has chemotherapeutic activity.
Kim
Jung-Mi
JM
Department of Food and Nutrition, Kyungnam University, Gyeongnam, Korea.
Park
Eunju
E
D019813:1,2-Dimethylhydrazine; D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D014451:Ubiquinone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C024989:coenzyme Q10; D019813:1,2-Dimethylhydrazine