ABSTRACT
OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.
ABSTRACT
Objective To investigate dynamic changes of heme oxygenase-1 and carbon monoxide in acute liver injury induced by carbon tetrach loride(CCl_4)in rats.Method Male SD rats were randomly allocated to induce acute liver injury by CCl_4 injection.Hepatic HO activity was examined at different time point following CCl_4 treatment.Expression and location of HO-1 protein was determined by western blot and immunohistochemical methods.Serum ALT,AST levels and hepatic SOD,MDA concentrations were also analyzed.Results Administration of CCl_4 to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels and liver MDA content combined with a remarkable reduction in liver SOD activity.HO activity was elevated significanfly in a time-dependant manner after CCl_4 injection,while the expression of HO-1 protein increased remarkably from 6 to 36 hours.CO concentration in the liver homogenate of control rats remained very low but was elevated significantly after CCl_4 treatment,which was in accordance with changes of HO-1. Conclusions HO-1 activity and protein expression as well as CO production are higher in rats with acute liver injury induced by CCl_4 than in control group.HO-1/CO system plays an important role in the pathogenesis of acute hepatic damage and may have potent protective effect against liver injury.