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AIM To investigate the protective effect of carnosic acid(CA) on the acute oxidative liver injury induced by thioacetamide (TAA) and explore its molecular mechanism from the pathway of PI3 K/Akt-Nrf2.METHODS Forty eight KM male mice were divided into six groups(n =8) : (A) control group; (B) carnosic acid group(130 mg·kg-1) ; (C) TAA group(50 mg·kg-1) ; (D)carnosic acid pretreatment group plus TAA; (E) D plus LY294002 treatment group (7 mg· kg-1) ; (F) D plus ZnPP treatment group (25 mg· kg-1).CA was administered orally to mice once a day for three consecutive days while the control group and TAA group received vehicle.One hour after the last treatment of CA, The mouse in group C, D, E, F were given intraperitoneal injection of TAA,group A and B were given vehicle ; 1 hr later, the group of E and F were given intraperitoneal injection of LY294002 and ZnPP respectively.18 hrs later, blood and liver tissue samples were collected.Biochemical evaluation includes the activities of serum transaminase, liver GSH, GSH-Px.Western blot analysis was employed to determine the expressions of HO-1, nuclear Nrf2, Keap1, Akt,Bcl-xL and caspase-3.RT-PCR analysis was employed to determine the gene expressions of HO-1, Nrt2, Bcl-xL and caspase-3.RESULTS TAA caused sever liver damage, while CA pretreatment provided hepatoprotection against TAA-induced liver injury,which could be observed from an improved liver histological structure, significant decrease of serum transaminase activities and inhibition of lipid peroxidation.CA also enhanced GSH-Px activities and attenuated glutathione depletion by TAA in liver.In addition, CA increased the nuclear translocation and expressions of Nrt2, HO-1 and p-Akt, while markedly reduced the level of Keap1 content.CA also increased the expression level of Bcl-xL and reduced the level of Caspase-3.LY294002 and ZnPP decreased the protective effect of CA.CONCLUSION CA increases the expression of HO-1 through PI3K/Akt-Nrf2 pathway and protects hepatocytes against the damage caused by TAA.This may be a primary mechanism of protective and antioxidative action of CA.