RESUMO
Liver is an important metabolic and detoxification organ in the body.Hepatic transporters are a series of functional membrane proteins that are extensively expressed in the liver.They are responsible for the uptake of endogenous and exogenous substances such as medicines into hepatocytes and excretion of their metabolic products into bile.Recent studies have provided that transporters and metabolic enzymes play important roles in the chemical substances-induced liver injury,and its various regulatory mechanisms have become hot topics of research.In this paper,we summarize the classification of hepatic transporters and metabolic enzymes and the changes of transporters and metabolic enzymes in the chemical substances-induced liver injury and its regulatory mechanism.
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.