RESUMO
BACKGROUND: The purpose of the present study was to compare the antioxidant potential of lipophilic tea polyphenols (LTP) against the one of naturally-occurring water-soluble green tea polyphenols (GTP) in a two-stage model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced hepatocarcinogenesis in Sprague-Dawley rats. MATERIALS AND METHODS: GTP/LTP was given 5-times weekly by oral gavage with tea polyphenols equivalent to 0-, 40- and 400-mg/kg of body weight/day. GTP/LTP treatment was started 2 weeks prior to the initiation of DEN and continued for 30 weeks. RESULTS: Histopathological and electron microscopic examination of liver tissue confirmed the protective effect of LTP on DEN/PB-induced liver damage and pre-carcinogenesis. LTP treatment significantly increased total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activity in liver tissues. Immunohistochemical detection of cellular nuclear factor erythroid-2-related factor-2 (Nrf2) and peroxiredoxin-6 (P6) indicated a down-regulation in Nrf2 and up-regulation of P6 expression in the liver of LTP-supplemented rats. CONCLUSION: The present study provides evidence for the first time, that LTP exerts significant antioxidant effects on DEN/PB-induced liver damage and hepatocarcinogenesis through elevating T-AOC levels, enhancing GSH-Px activity and inducing P6 expression in rat liver tissues.
Assuntos
Antioxidantes/farmacologia , Carcinógenos , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/efeitos dos fármacos , Dietilnitrosamina/efeitos adversos , Fenobarbital/efeitos adversos , Polifenóis/farmacologia , Chá/química , Animais , Antioxidantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Peroxirredoxina VI/genética , Peroxirredoxina VI/metabolismo , Polifenóis/administração & dosagem , RatosRESUMO
BACKGROUND: Green tea polyphenols (GTPs) have been proposed as promising candidates for chemoprevention. However, GTPs levels are maintained relatively low in the blood and are chemically-unstable. Lipid-soluble tea polyphenols (LTPs) are products of modified GTPs with ester linkage with fatty acids. LTPs are lipophilic and expected to provide improved absorption and utilization in the body compared with water-soluble polyphenols. The current study was designed to investigate the chemo-preventive property and the possible mechanisms of LTP action against diethylnitrosamine (DEN)-induced liver cancer in rats. MATERIALS AND METHODS: Oral administration of LTPs at doses of 0, 40, and 400 mg/kg/day was initiated 2 weeks prior to DEN injection and was continued for 30 weeks. At that time point samples were collected and liver histopathological analyses were performed. RESULTS: LTPs decreased the area and number of placental glutathione S-transferase-positive foci in liver samples of DEN-treated rats. Furthermore, LTPs counteracted DEN-induced fibrosis formation in liver. Immunohistochemical staining of rat liver showed that LTPs inhibited DEN-mediated elevations in numbers of cells positive for PCNA and 8-OHdG. CONCLUSION: For the first time, the present study demonstrated, that LTPs exert a chemo-preventive effect against precancerous lesions through inhibition of cellular proliferation and DNA damage in a rat liver model.
