RESUMO
Phyllanthus orbicularis HBK (Euphorbiaceae) is a medicinal plant, endemic to Cuba, whose aqueous extract has proven antimutagenic effects against hydrogen peroxide and some promutagenic aromatic amines (AAs), in addition to its antiviral properties. In this paper, antimutagenesis of this extract against two carcinogenic AAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 4-aminobiphenyl (4-ABP) has been studied. Liver microsomal fractions from both induced rats and humans were used to metabolise both procarcinogenic compounds in the Salmonella assay. The plant extract was effective in reducing the mutagenesis of these AAs, activated by both kinds of fractions. The optimal antimutagenic effect was obtained when both AAs were metabolised by human enzymes, with an almost total reduction of 4-ABP mutagenesis and a decrease of about 75% of PhIP mutagenicity. Mutagenicity of both AAs, activated by induced rat fraction, was only decreased by about 50%. Inhibition by plant extract of alkoxyresorufin O-dealkylation activities, dependent on CYP1A, of both fractions was determined. In accordance with the results obtained, the inhibition or modulation of CYP1A subfamily activities, and possibly of CYP1A2, is thought to be the main mechanism of antimutagenesis of the aqueous extract of Phyllanthus orbicularis against 4-ABP and PhIP.
Assuntos
Compostos de Aminobifenil/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Imidazóis/metabolismo , Phyllanthus , Animais , Relação Dose-Resposta a Droga , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta , RatosRESUMO
Phyllanthus orbicularis HBK is an endemic Cuban plant whose aqueous extract has been proposed as an effective drug for the treatment of viral diseases. In addition, antimutagenic properties of this extract have also been reported. In the present study, the genotoxicity of this plant extract was assessed using different in vitro and in vivo assays. Results from SOS gene induction, gene reversion and conversion, and SMART assays clearly show that P. orbicularis aqueous extract does not induce either primary DNA damage or mutation. Additionally, no statistically significant difference was found in the percentage of chromosomal aberrations in Chinese hamster ovarian (CHO) cells treated with the plant extract. On the contrary, micronuclei and abnormal anaphase were induced by this extract in CHO cells. This genotoxic effect was related to a high cytotoxicity. Single spots were detected in the SMART assay. These results point to a possible aneugenic effect of the P. orbicularis aqueous extract at cytotoxic doses which are much higher than those seen by their antiviral and antimutagenic activities.
Assuntos
Mutação/efeitos dos fármacos , Phyllanthus/toxicidade , Extratos Vegetais/toxicidade , Anáfase/efeitos dos fármacos , Animais , Células CHO , Aberrações Cromossômicas/efeitos dos fármacos , Cricetinae , DNA/análise , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Relação Dose-Resposta a Droga , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Feminino , Testes de Mutagenicidade , Mutação/genética , Resposta SOS em Genética/efeitos dos fármacos , Resposta SOS em Genética/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
Phyllanthus orbicularis is a medicinal plant, endemic to Cuba, whose aqueous extract has proven antiviral properties and antimutagenic activities against aromatic amines and hydrogen peroxide. In addition, this plant extract presents antioxidant activity. In this paper, using the Salmonella assay with the experimental approaches of co-incubation, pre- and post-treatments, it is shown that the P. orbicularis extract protects bacterial cells from oxidative damage and mutation by some intracellular mechanism, irrespective of its antioxidant activity.
