title: 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.
abstract: 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.
authors.affiliation: Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, 608 002, India.
authors.forename: R
authors.initials: R
authors.lastname: Vinothkumar
authors.forename: M
authors.initials: M
authors.lastname: Sudha
authors.forename: P
authors.initials: P
authors.lastname: Viswanathan
authors.forename: J
authors.initials: J
authors.lastname: Kabalimoorthy
authors.forename: T
authors.initials: T
authors.lastname: Balasubramanian
authors.forename: N
authors.initials: N
authors.lastname: Nalini
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000009:adverse effects; D058739:Aberrant Crypt Foci / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018890:Chemoprevention / Q000379:methods; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000081005:Cyclohexane Monoterpenes; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000502:physiology; D008962:Models, Theoretical; D039821:Monoterpenes / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; C006923:carvone; D013482:Superoxide Dismutase; D005978:Glutathione; D019813:1,2-Dimethylhydrazine