Objective:To study the role of the heme oxygenase-1(HO-1)in rifampicin(RFP)induced liver oxidative stress injury.Methods:(1)In vivo experiments:Balb/c mice were randomly divided into three groups(n=8)

including normal saline(NS)control group

DMSO control group

rifampicin(RFP) model group(200 mg/kg)

respectively. Levels of serum total bilirubin(TB)

alanine aminotransferase(ALT)

aspartate aminotransferase(AST)

and malondialdehyde(MDA)

glutathione peroxidase(GSH-Px)

superoxide dismutase(SOD)of mice liver homogenates were determined after gavage for 15 days. Pathological morphology changes were observed with HE staining and the expression of HO-1 protein was measured by Western blot.(2)In vitro experiments:different concentrations(10 μmol/L

50 μmol/L

100 μmol/L)of rifampicin were implemented in Hep G2 cells for 24

48

72 h

respectively. Proliferation of cells was tested by CCK-8 Kit

and the levels of ALT

AST in supernatant and MDA

SOD and GSH-Px in cell extracted proteins were determined. The expression of HO-1 protein was examined via Western blot. Results :Compared with DMSO control group and NS control group

rifampin group showed a significantly higher levels of total bilirubin(F=64.002

P=0.000)

AST(F=37.046

P=0.000)

ALT(F=64.706

P=0.000)

MDA(F=10.777

P=0.001)

as well as a notable decrease of GSH-Px(F=40.962

P=0.000)

SOD(F=83.165

P=0.000). Furthermore

the jaundice

hepatomegaly and hydropic degeneration of hepatocytes surrounding the central vein could be found in RFP group. CCK-8 detection showed that cytotoxicity induced by rifampicin was in a time and concentration dependant manner in Hep G2 cell line. The levels of AST

ALT

MDA were elevated significantly

on the contrary

the activity of GSH-Px

SOD were decreased in RFP groups. At last

the HO-1 expression was significantly upregulated in rifampicin treated group via Western blot analysis in vitro and in vivo. Conclusion:RFP could induce oxidative stress injury in liver

and the upregulation of HO-1 expression is correlated with development of the liver injury.