RESUMO
The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bile duct ligation (BDL)-induced hepatic fibrosis in rats. BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days. Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-ß1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO). The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson's trichrome stain. ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group. These elevations were significantly decreased by BC703 treatment. Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group. In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment. Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-ß1. Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat. BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease.
Assuntos
Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Platycodon , Substâncias Protetoras/uso terapêutico , Animais , Ductos Biliares/cirurgia , Colestase/tratamento farmacológico , Colestase/metabolismo , Glutationa/metabolismo , Ligadura , Cirrose Hepática/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Raízes de Plantas , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Crescimento Transformador beta1/sangueAssuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Coelhos/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Disponibilidade Biológica , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Cromatografia Líquida/veterinária , Estudos Cross-Over , Meia-Vida , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Modelos Lineares , MasculinoAssuntos
Antibacterianos/farmacocinética , Linguado/metabolismo , Tianfenicol/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Tianfenicol/administração & dosagem , Tianfenicol/farmacocinéticaRESUMO
We investigated the effects of hepatic and renal impairment on the pharmacokinetics of enrofloxacin in Sprague-Dawley rats. Experimental hepatic and renal failure were induced by carbon tetrachloride (CCL(4)) and 5/6 nephrectomy, respectively. After intravenous dosing of enrofloxacin (10 mg/kg), plasma concentrations of enrofloxacin were measured using liquid chromatograph/mass spectrometry. There was no significant effect of hepatic impairment on enrofloxacin pharmacokinetics. However, renal impairment markedly prolonged elimination half life (t(1/2lambdaz)) of enrofloxacin (P < 0.05), comparing with respective control. Total body clearance (Cl(b)) and volume of distribution at steady state (V(ss)) were significantly decreased (P < 0.05) by renal impairment. In conclusion, these results suggested that renal impairment could affect the pharmacokinetics of enrofloxacin.