Objective:To investigate the protective effects of baicalin on liver in hepatic precancerous mice induced by diethylnitrosamine(DEN).Methods:Hepatic precancerous model was obtained by administration of DEN through intraperitoneal injection to male mice,and the pharmacologic effects of baicalin were assayed by histopathologic examination and levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),gultathione-S-transferases(GST) and alkaline phosphatase (ALP).Results:The liver functions were serious damaged by administration of DEN,which showed up as morphologic changes and abnormal structure in model mice,such as hver cirrhosis,hepatic fibrosis which divided the liver lobule,liver cell denaturation, hyperplasia,intranuclear inclusions and tendency to atypia,and heavy local infiltration by macrophages was observed,at the same time,enzymatic activities in serum were increased abnormally(P0.05).Situations of mice treated by baicalin were much better,and hepatic fibrosis was decreased,which was failed to divide the liver lobule,and scarce liver cell denaturation,atypical hyperplasia,intranuclear inclusions could be observed.Enzymatic activities in serum were decreased markedly compared with those in model mice(P0.05).Conclusion:Baicalin is partly effective to protect the liver functions in hepatic precancerous mice induced by DEN.
Context: Pharmacokinetics of drug may be altered by abnormal physiological functions in illness, which will affect its pharmacodynamic efficacy in turn.Objective: To assess the preventive effects of tetramethylpyrazine (TMPZ) phosphate on hepatocarcinogenesis and its pharmacokinetic differentiations in model mice.Methods: Diethylnitrosamine (DEN) was adopted to induce hepatic precancerous model in mice through intraperitoneal injection, and prevention efficacy of TMPZ at a dose of 162 mg/kg was examined by liver histological analysis and activities of serum marker enzymes. Pharmacokinetic variations of TMPZ between control and model mice were measured for single oral administration.Results: DEN initiation led to a remarkable increase of serum marker enzymes, and abnormality such as bile canaliculi hyperplasia and presence of tumor cells were observed in liver histopathological examination in model mice, while the control ones revealed normal architecture. Oral treatment of TMPZ resulted in a marked reduction in serum marker enzymes and improvement in liver histopathology compared with model ones. In pharmacokinetic study, values of AUC and T-max of TMPZ became significantly greater with increase of doses in both control and model mice, which elucidated the absorption was enhanced and delayed; meanwhile, its elimination was not affected markedly. When the mice were treated at same dose, the adsorption of TMPZ in model mice was greatly improved than that in control ones, while T-max and MRT had no significant difference.Conclusion: TMPZ was partly effective to protect liver from carcinogenesis initiated by DEN, and hepatic insufficiency could change its pharmacokinetics.