RESUMO
Stem bark of Erythrina latissima E. Mey (Leguminosae) contains a wide range of prenylated flavonoids able to counteract the genotoxic properties of aflatoxin B1 (AFB1). Thus, the hypothesis was raised that E. latissima stem bark extracts (ELBE) may counteract the in vivo hepatotoxic effects of aflatoxins, contaminants in food and feed. An HPLC-DAD method was developed and validated to determine the level of flavonoid aglycones (11.82%) and glycosides (16.17%). ADME, pharmacokinetic and drug-likeness assessment of major flavonoids of ELBE, using the web tool SwissADME, showed good oral bioavailability. The protective effect of ELBE against AFB1 induced genotoxicity in the Vitotox assay after metabolic activation was confirmed (IC50 of 44.32⯵g/ml), followed by evaluation of its inhibitory effect on hepatotoxicity in rats induced by the same agent. Male Wistar rats were orally treated with ELBE (20â¯mg/kg, 50â¯mg/kg and 100â¯mg/kg) or curcumin (500â¯mg/kg) combined with piperine (20â¯mg/kg) - positive control, for 8 days prior to AFB1 exposure (1â¯mg/kg). The ELBE group showed a decreased activity of ALP and γ-GT compared to the AFB1 group. Histopathological examination of the liver demonstrated ameliorative effects of ELBE. Thus, ELBE could have a protective effect against hepatotoxins such as AFB1.
Assuntos
Aflatoxina B1/toxicidade , Antimutagênicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Erythrina/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Animais , Antimutagênicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Flavonoides/análise , Masculino , Extratos Vegetais/química , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
South African herbal teas, rooibos and honeybush, are increasingly enjoyed as healthy alternatives to Camellia sinensis teas. They contribute to the diet with bioactive phytochemicals not commonly found in foods. Major compounds of rooibos are the unique dihydrochalcone, aspalathin, and its flavone isomers, orientin and isoorientin. Honeybush contributes the xanthones, mangiferin and isomangiferin and the flavanones, eriocitrin, narirutin and hesperidin. All these compounds are either C-glucosides or O-rhamnoglucosides, which are poorly absorbed. Phase II metabolism and degradation by intestinal bacteria are important factors in their absorption. Modulation of drug metabolising enzymes is indicated which not only could affect the therapeutic window of drugs, but also the bioavailability of other dietary flavonoids.
Assuntos
Bebidas , Dieta , Fenóis/farmacocinética , Antimutagênicos/química , Antimutagênicos/farmacocinética , Antimutagênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Aspalathus/química , Disponibilidade Biológica , Cyclopia (Planta)/química , Interações Ervas-Drogas , Fenóis/química , Fenóis/farmacologia , África do SulAssuntos
Antimutagênicos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Mutagênicos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , 4-Nitroquinolina-1-Óxido/toxicidade , Animais , Antracenos/toxicidade , Antimutagênicos/farmacocinética , Biotransformação , Fluorenos/toxicidade , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Testes de Mutagenicidade , Mutagênicos/farmacocinética , Mutagênicos/toxicidade , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Ratos , Salmonella typhimurium/genéticaRESUMO
The anticarcinogenic effects of beta-carotene (BC) have been extensively investigated, but only in vitro assays have examined the ability of BC to modulate gene mutation. In view of the current interest in the provitamin as a cancer chemopreventive agent, and the association between mutagenesis and carcinogenesis, we have dosed Fischer 344 rats with model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated the relationships among BC intake, its tissue accumulation, and antimutagen activity. Animals received drinking water supplemented with BC at doses of 0-0.25% ad libitum, using three dosing schedules. In one group BC dosing commenced before, and continued for three alternating weeks after i.p. injection of 100 mg ENU/kg; another group was given BC only after mutagen treatment. Animals from the first two groups were sacrificed 5 weeks post-mutagen treatment, and cells were isolated from the spleen to determine the frequency of 6-thioguanine- resistant (6-TGr) T-lymphocytes. The presence of BC caused a reduction in the frequency of 6-TGr T-cells produced by ENU, but the inhibition was non-linear within the range of BC doses used. BC intake only after mutagen treatment was more effective than the combination of pre- and post-mutagen intake. In the third group, rats were treated with 100 mg ENU/kg, and BC administration was continued at a fixed dose of 0.15% in the drinking water for 2, 4, 6, or 8 weeks. Measurement of the frequency of 6-TGr T-cells at the end of the specified times showed > 50% reduction in ENU-mediated mutagenicity throughout the experiment. Analysis of BC levels in the liver and in the spleen following BC intake before and during mutagen exposure revealed higher levels than when BC was given only after mutagen treatment. Continuous intake of BC also showed increased tissue levels. There were some correlations observed between BC tissue levels and the antimutagenic effects for the first two groups, but these correlations were not statistically significant, possibly due to the small numbers of animals used. Taken together, the results demonstrate that intact BC is absorbed, stored, and exerted antimutagenic effects against a chemical carcinogen in rats without first being transformed to retinol in the gastrointestinal tract.
Assuntos
Antimutagênicos/farmacologia , Carotenoides/farmacologia , Linfócitos/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Antimutagênicos/farmacocinética , Carotenoides/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas , Etilnitrosoureia , Fígado/metabolismo , Linfócitos/metabolismo , Masculino , Mutagênicos , Ratos , Ratos Endogâmicos F344 , Baço/metabolismo , Distribuição Tecidual , beta CarotenoRESUMO
Sixty-two Egyptian food and medicinal preparations were extensively examined for antimutagenic/anticarcinogenic activity using short-term and host-mediated assays. The antimutagenic activity of the substances examined was ranked as follows: thirteen (strong), seven (mild) and five (weak) after metabolic activation. Metabolic activation seems to be necessary for most antimutagenic substances in this study, e.g. radish inhibits 29% of mutagenicity produced in direct antimutagenic assay and inhibits 89% of mutagenicity induced in host-mediated assay.
Assuntos
Anticarcinógenos/farmacologia , Antimutagênicos/farmacologia , Alimentos , Plantas Medicinais , Animais , Anticarcinógenos/farmacocinética , Antimutagênicos/farmacocinética , Biotransformação , Egito , Camundongos , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologiaRESUMO
The influence of vitamin E on the mutagenic activities of aflatoxin and adriamycin was studied. The results indicate that vitamin E shows antimutagenic activity towards aflatoxin B1 only when homogenized with liver tissue.