Zoledronic acid prevents the hepatic changes associated with high fat diet in rats; the potential role of mevalonic acid pathway in nonalcoholic steatohepatitis.

摘要: Abstract The role of hepatic free cholesterol (FC) in nonalcoholic steatohepatitis (NASH) is raised up and the intervention with synthesis will be a potential therapeutic target. This study investigated hepatoprotective effect mevalonic acid pathway inhibition by Zoledronic (ZA) on changes associated high fat diet (HFD) rats.Thirty two male Wistar rats were used. They divided into 2 groups: (I) control naive (II) NASH: induced HFD for 12 weeks, this group subdivided (A) NASH untreated (B)NASH + ZA (50ug/kg/week) i.p. weeks (C) NASH + ZA (100μg/kg/week) weeks. Portal pressure (PP), liver enzymes AST ALT, serum glucose, lipid profile, levels tumor necrosis factor alpha (TNF-α), vascular endothelial growth (VEGF), FC triglyceride (TG), histopathological expression both smooth muscle actin (α-SMA) Caspase-3 measured. ZA significantly prevented portal hypertension, worsening function, dyslipidemia. TNF-α, VEGF, TG decreased comparison to group. hindered HFD. inhibited α-SMA significant difference favor dose intervention. related manner prevents pathological effects chronic ingestion rats. may largely mediated its ability reduce TNF-α FC.