RESUMO
OBJECTIVE: To investigate the mechanism of the different levels of serum bisphenol A (BPA) between rat and mouse after oral administration. METHODS: A total of 18 specific pathogen free (SPF) male rats and 18 mice were treated with 300 mg/kg BPA by oral administration, blood samples were taken from rats and mice after BPA administration at 0.5, 1.0, 12.0 h time points (n = 6 at each point). Serum BPA levels were quantified using fluorescence-high performance liquid chromatography (FL-HPLC) analysis. The rats and mice (n = 6, respectively) were perfused with 100 ml of 0.1 mmol/L BPA by intestinal absorption in situ, then the BPA levels of perfusion fluid at 0.5, 1.0, 2.0 h time points and serum at 2.0 h after BPA perfusion were determined by FL-HPLC analysis. The levels of UDP-glucuronosyltransferase 2B1 (UGT2B1) mRNA expression in the liver of rats and mice were analyzed by semi-quantitative RT-PCR and UGT2B1 enzymatic activity was determined by FL-HPLC method. The rats and mice (n = 6, respectively) were treated with 300 mg/kg BPA by oral administration after fasting 24 h, the feces were collected during 24 h and the levels of BPA in feces were determined by FL-HPLC analysis. RESULTS: At 0.5, 1.0, 12.0 h after oral administration at 300 mg/kg BPA, the levels of serum BPA in mice ((66.57 ± 14.95), (51.16 ± 16.06), (22.73 ± 5.00) µg/ml, respectively) were significantly higher than in rats ((15.63 ± 5.65), (18.34 ± 5.02), (7.65 ± 2.58) µg/ml, respectively) (F values were 50.660, 17.957, 8.420, respectively, P < 0.05), the rates of absorption in mice small intestine during 0 h-, 0.5 h-, 1.0 - 2.0 h ((10.20 ± 4.20), (1.49 ± 0.67), (1.31 ± 0.55) µg × cm(-2) × min(-1), respectively) were higher than that in rats ((1.87 ± 0.69), (0.47 ± 0.13), (0.36 ± 0.08) µg × cm(-2) × min(-1), respectively) (F values were 14.954, 8.877, 11.536, respectively, P < 0.05), the serum BPA levels in mice ((22.64 ± 4.35) µg/ml) were significantly higher than in rats ((4.13 ± 0.83) µg/ml) after 2 h perfusion with 0.1 mmol/L BPA (F = 74.643, P = 0.000), the levels of UGT2B1 mRNA expression and enzymatic activity in the rats liver were obviously higher than in the mice liver. After oral administration at 300 mg/kg BPA, the feces BPA levels of rats ((1.50 ± 0.32) mg/g) were significantly higher than that of the mice ((0.57 ± 0.35) mg/g) (F = 21.215, P = 0.001) during 24 h. CONCLUSION: The serum BPA level of mouse is significantly higher than the rat after oral administration at 300 mg/kg BPA, which may be caused by BPA high absorption rate of mouse small intestine and strong ability of BPA glucuronidation and excretion of the rat.
Assuntos
Camundongos Endogâmicos ICR/metabolismo , Fenóis/sangue , Fenóis/metabolismo , Ratos Sprague-Dawley/metabolismo , Animais , Compostos Benzidrílicos , Absorção Intestinal , Dose Letal Mediana , Masculino , Camundongos , Fenóis/toxicidade , RatosRESUMO
OBJECTIVE: To investigate the relationship of time-concentration of bisphenol A (BPA) in male Sprague-Dawley (SD) rats after single oral BPA administration. METHODS: A total of 66 specific pathogen free (SPF) SD male rats were divided into 10 experimental groups and control group (n = 6). The experimental group rats were treated with BPA of 300 mg/kg by oral gavage and blood samples were taken from one group at 0.5, 1, 2, 4, 6, 12, 24, 36, 60, 84 h time point after oral administration, respectively. The serum BPA concentration was determined by fluorescence-high performance liquid chromatography (FL-HPLC) analysis. RESULTS: After oral administration of 300 mg/kg, the total serum BPA concentration of 17.13 microg/ml was the highest in rats at 1 h, then decreased, but it increased to 15.18 microg/ml again at 24 h, then gradually decreased to 0.51 microg/ml at 84 h. The level of serum free BPA was lower than that of total serum BPA after oral administration, the serum free BPA was 0.57 microg/ml at 0.5 h after oral administration. The serum free BPA level decreased to 0.06 microg/ml at 1 h, 0.03 microg/ml at 4 h, 0.01 microg/ml at 36 h after oral administration. The free BPA was only 4.15% (0.57/13.73) in total BPA in serum at 0.5 h after oral administration of 300 mg/kg BPA. CONCLUSION: These results suggested that conjugated BPA was the main metabolite of BPA in rat serum after single oral administration. Enterohepatic circulation of BPA glucuronide in rats may results in two peak levels of total BPA in serum.