title: Black tea polyphenols modulate xenobiotic-metabolizing enzymes, oxidative stress and adduct formation in a rat hepatocarcinogenesis model.
abstract: The present study was designed to investigate the modulatory effects of black tea polyphenols (Polyphenon-B) on phase I and phase II xenobiotic-metabolizing enzymes and oxidative stress in a rat model of hepatocellular carcinoma (HCC). Liver tumours induced in male Sprague-Dawley rats by dietary administration of rho-dimethylaminoazobenzene (DAB) increased cytochrome P450 (total and CYP1A1, 1A2 and 2B isoforms), cytochrome b(5), cytochrome b(5) reductase, glutathione S-transferase (GST total and GST-P isoform) and gamma-glutamyltranspeptidase (GGT) with decrease in quinone reductase (QR). This was accompanied by enhanced lipid and protein oxidation and compromised antioxidant defences associated with increased expression of the oxidative stress markers 4-hydroxynonenal (4-HNE), anti-hexanoyl lysine (HEL), dibromotyrosine (DiBrY) and 8-hydroxy 2-deoxyguanosine (8-OHdG). Dietary administration of Polyphenon-B effectively suppressed DAB-induced hepatocarcinogenesis, as evidenced by reduced preneoplastic and neoplastic lesions, modulation of xenobiotic-metabolizing enzymes and amelioration of oxidative stress. Thus, it can be concluded that Polyphenon-B acts as an effective chemopreventive agent by modulating xenobiotic-metabolizing enzymes and mitigating oxidative stress in an in vivo model of hepatocarcinogenesis.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
authors.forename: Ramalingam Senthil
authors.initials: RS
authors.lastname: Murugan
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Siddavaram
authors.initials: S
authors.lastname: Nagini
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D028241:Camellia sinensis / Q000737:chemistry; D018736:DNA Adducts / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015262:Xenobiotics / Q000378:metabolism*; D004124:p-Dimethylaminoazobenzene
chemical_list: D016588:Anticarcinogenic Agents; D015415:Biomarkers; D018736:DNA Adducts; D004798:Enzymes; D010636:Phenols; D015262:Xenobiotics; C506663:polyphenon B; D004124:p-Dimethylaminoazobenzene