Coenzyme Q10 attenuated DMH-induced precancerous lesions in SD rats

J Nutr Sci Vitaminol (Tokyo). 2010;56(2):139-44. doi: 10.3177/jnsv.56.139.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine
  • Analysis of Variance
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antioxidants / pharmacology
  • Colon / drug effects
  • Colon / metabolism
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • DNA Damage / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology

Substances

  • Anticarcinogenic Agents
  • Antioxidants
  • Ubiquinone
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • coenzyme Q10
  • 1,2-Dimethylhydrazine