Black tea polyphenols modulate xenobiotic-metabolizing enzymes, oxidative stress and adduct formation in a rat hepatocarcinogenesis model.
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.
Murugan
Ramalingam Senthil
RS
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
Uchida
Koji
K
Hara
Yukihiko
Y
Nagini
Siddavaram
S
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
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D018736:DNA Adducts; D004798:Enzymes; D010636:Phenols; D015262:Xenobiotics; C506663:polyphenon B; D004124:p-Dimethylaminoazobenzene