title: Modulatory effect of troxerutin on biotransforming enzymes and preneoplasic lesions induced by 1,2-dimethylhydrazine in rat colon carcinogenesis.
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 β-glucronidase, β-glucosidase, β-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.
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors: Rajamanickam
authors: R
authors: Vinothkumar
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors: Rajenderan
authors: R
authors: Vinoth Kumar
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors: Mani
authors: M
authors: Sudha
authors: Department of Pathology, Rajah Muthiah Medical College, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors: Periyaswamy
authors: P
authors: Viswanathan
authors: Faculty of Marine Sciences, Centre for Advanced Study in Marine Biology, Annamalai University, Parangipettai 608 502, Tamil Nadu, India.
authors: Thangavel
authors: T
authors: Balasubramanian
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India. Electronic address: nalininam@yahoo.com.
authors: Namasivayam
authors: N
authors: Nalini
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001711:Biotransformation / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000925:Anticoagulants; D002273:Carcinogens; D006896:Hydroxyethylrutoside; C005865:troxerutin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D019813:1,2-Dimethylhydrazine
keywords: 1, 2-dimethylhydrazine; Aberrant crypt foci; Bacterial enzymes; Colon cancer; Troxerutin; Xenobiotic enzymes