The heat shock protein 90 inhibitor,17-AAG,attenuates thioacetamide induced liver fibrosis in mice

Background heat shock protein 90 (hsp90) is proposed to be involved in liver disorders. this study was conducted to test effect of 17-n-allylamino-17-demethoxygeldanamycin (17-aag),an inhibitor of hsp90,on attenuating thioacetamide induced liver fibrosis in vivo. methods four groups of swiss albino male mice (cd-1 strain) were used as follows: control group; thioacetamide group (received 100 mg/kg thioacetamide,ip injection,3 times/week for 8 weeks); thioacetamide plus 17-aag groups (received 100 mg/kg thioacetamide,ip injection,3 times/week for 8 weeks plus 25 or 50 mg/kg 17-aag,ip injection,5 days/week along the last 4 weeks). fibrosis was quantified by measuring hydroxyproline level and by morphometry and oxidative stress biomarkers were assigned. relative hepatic mrna expressions of α-smooth muscle actin (α-sma),collagen-1-alpha-1 (col1a1) and tissue inhibitor metalloproteinase-1 (timp-1) mrnas were measured by rt-pcr. levels of the apoptotic markers caspase-3,factor related apoptosis (fas) and hsp-90 were assigned in tissue homogenate. results 17-aag (50 mg/kg) significantly decreased fibrosis percentage significantly (p < 0.001,0.05) compared to thioaceatmide and 25 mg/kg,respectively. malondialdehyde,hsp90,α-sma,col1a1 and timp-1 expression levels were significantly reduced (p < 0.05) by the inhibitor large dose. levels of gsh,caspase-3 and fas were markedly (p < 0.001) increased in the group received 17-aag (50 mg/kg) compared to other groups. conclusion the hsp90 inhibitor,17-aag,can attenuate thioacetamide hepatotoxicity through oxidative stress counterbalance,reducing stellate cells activity and inducing apoptosis. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.