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Exp Mol Pathol ; 96(1): 15-26, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24512697

ABSTRACT

Colon cancer is the third most global oncologic problem faced by medical fraternity. Troxerutin, a flavonoid present in tea, coffee, cereal grains, and a variety of fruits and vegetables, exhibits various pharmacological and biological activities. This study was carried out to investigate the effect of troxerutin on xenobiotic metabolizing enzymes, colonic bacterial enzymes and the development of aberrant crypt foci (ACF) during 1,2-dimethylhydrazine (DMH) induced experimental rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control. Group 2 received troxerutin (50 mg/kg b.w., p.o. every day) for 16 weeks. Groups 3-6 received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups 4-6 received different doses of troxerutin (12.5, 25, 50 mg/kg b.w., p.o. every day respectively) along with DMH injections. Our results reveal that DMH treated rats exhibited elevated activities of phase I enzymes such as cytochrome P450, cytochrome b5, cytochrome P4502E1, NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase and reduced activities of phase II enzymes such as glutathione-S-transferase (GST), DT-diaphorase (DTD) and uridine diphospho glucuronyl transferase (UDPGT) in the liver and colonic mucosa of control and experimental rats. Furthermore, the activities of fecal and colonic mucosal bacterial enzymes, such as ß-glucronidase, ß-glucosidase, ß-galactosidase and mucinase were found to be significantly higher in DMH alone treated rats than those of the control rats. On supplementation with troxerutin to DMH treated rats, the alterations in the activities of the biotransforming enzymes, bacterial enzymes and the pathological changes were significantly reversed, the effect being more pronounced when troxerutin was supplemented at the dose of 25 mg/kg b.w. Thus troxerutin could be considered as a good chemopreventive agent against the formation of preneoplastic lesions in a rat model of colon carcinogenesis.


Subject(s)
1,2-Dimethylhydrazine/toxicity , Aberrant Crypt Foci/drug therapy , Biotransformation/drug effects , Cell Transformation, Neoplastic/pathology , Colonic Neoplasms/drug therapy , Hydroxyethylrutoside/analogs & derivatives , Aberrant Crypt Foci/chemically induced , Aberrant Crypt Foci/enzymology , Animals , Anticoagulants/therapeutic use , Carcinogens/toxicity , Cell Transformation, Neoplastic/chemically induced , Colonic Neoplasms/chemically induced , Colonic Neoplasms/enzymology , Cytochrome P-450 Enzyme System/drug effects , Cytochrome P-450 Enzyme System/metabolism , Glucuronosyltransferase/drug effects , Glucuronosyltransferase/metabolism , Glutathione Transferase/drug effects , Glutathione Transferase/metabolism , Hydroxyethylrutoside/therapeutic use , Male , Oxidoreductases/drug effects , Oxidoreductases/metabolism , Rats , Rats, Wistar
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