RESUMO
Objective: To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot (TFA) against α-naphthylisothiocyanate (ANIT)-induced cholestasis. Methods: The hepatoprotective activities of TFA (125, 250 and 500 mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic mRNA and protein levels of transports, multidrug resistance-associated protein 2 (MRP2), bile salt export pump (BSEP), and Na+-taurocholate cotransporting polypeptide (NTCP) were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results: Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and mRNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion: TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.
RESUMO
Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra (PRR) at different doses against α-naphthylisothiocyanate (α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig administrated with vehicle or PRR [(1,9,18,36,54,72,and 81 g/(kg·d)] 3 d before and 2 d after α-NIT (60 mg/kg) ig administration.The general status of rats,histopathology of liver,serum alanine aminotransaminase,aspartate aminotransaminase,total bilirubin,direct bilirubin,and alkaline phosphatase levels,were observed at respective time points (24 and 48 h) after α-NIT administration.Using cluster analysis and correspondence analysis,the dose-effect-response relationships of PRR were evaluated.Results The results showed that compared with model group,the serum biochemistry index significantly decreased with the increasing of PRR dosage (P ＜ 0.01),and the change and necrosis of hepatic cellula,and inflammatory cell infiltration were gradually alleviated.However,the improvement was not obviously found in the low-dose group [1 g/(kg·d)].The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorate α-NIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner.Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect,especially in the treatment of heavy acute cholestasis hepatitis.