Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice.

摘要: Background & Aims Oltipraz (4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione), a promising cancer preventive agent, has an antioxidative activity and ability to enhance glutathione biosynthesis, phase II detoxification enzymes multidrug resistance-associated protein-mediated efflux transporters. can protect against hepatotoxicity caused by carbon tetrachloride, acetaminophen alpha-naphthylisothiocyanate. Whether oltipraz hepato-protective effects on obstructive cholestasis is unknown. Methods We administered mice for 5days prior bile duct ligation (BDL) 3days. Liver histology, liver function markers, flow rates hepatic expression of profibrogenic genes were evaluated. Results Mice pretreated with BDL demonstrated higher levels serum aminotransferases more severe damage than in control mice. Higher secretion observed unoperated treated mice, suggesting that necrosis oltipraz-treated may be related partially increased bile-acid independent biliary pressure. treatment enhanced α-smooth muscle actin expression, consistent activation stellate cells portal fibroblasts. Matrix metalloproteinases (Mmp) 9 13 tissue inhibitors (Timp) 1 2 the group, secondary injury induced might due excessive Mmp Timp secretions, which induce remodeling extracellular matrix. Conclusions exacerbates severity following should avoided as therapy extrahepatic cholestatic disorders obstruction.