Objective: To study the effect of 999 Ganmaoling on rat liver and compare the effect of Ganmaoling on the enzyme activity of CYP2E1 in different species of rats

mice and humans

so as to provide the experimental basis for the clinical safety reevaluation and rational use. Method: Rats were divided into two groups:blank control and Ganmaoling group

which were administrated respectively with 0.5% CMC-Na or equal volume of Ganmaoling at the dose of 4.53 g·kg-1 for oral administration. The rats were weighed after 14 d

and then treated the next day. Activity of serum alanine aminotransferase (ALT)

aspartate aminotransferase (AST)

creatine kinase (CK)

urea nitrogen (BUN) and creatinine (SCr) were detected by automatic biochemical analyzer. The liver

kidney and heart were collected. The ratio of tissue weight to body weight was counted. HE staining was used in the slices of liver sample

and the histopathological change in liver was observed by light microscopy. Human

rat and mouse liver microsomes were incubated respectively with different concentrations of Ganmaoling or APAP at 37℃ for 15 minutes

then chlorzoxazone

as CYP2E1 probe substrate

and nicotinamide adenosine denucleotide hydro-phosphoric acid (NADPH) were added and incubated for another 30 minutes. The content of 6-hydroxychlorzoxazone was detected by LC-MS/MS method. The inhibition rate concentration(IC50) was calculated. Result: Compared with blank control group

the liver

kidney and heart weight index

serum biochemical indicators

and liver histopathology in Ganmaoling group showed no significant change. The IC50 values of Ganmaoling for CYP2E1 in liver microsomes of human

rat and mouse were 6.516

344.2

932.8 mg·L-1 respectively. The IC50 values of APAP for CYP2E1 in human

rat

and mouse liver microsomes were 52.4

453.8

806.5 mg·L-1

respectively. Ganmaoling and APAP showed a consistent trend of inhibition of CYP2E1 in various genera. Conclusion: The order of the inhibitory activity of Ganmaoling against CYP2E1 of different species from high to low was human

mouse and rat. The difference may explain the reason that large-dose Ganmaoling has no obvious toxicity to rat liver. The results suggest that different species of animals shall be adopted in drug pre-clinical safety assessments

especially for the study of effect on liver metabolism. In clinical practice

more attention shall be paid to the interaction between compound cold medicine containing APAP and other drugs

in order to provide the basis for rational clinical drug use.