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      • LC, Acute : O-055 ; Protection from liver fibrosis by a PPAR agonist

        ( Keiko Iwaisako ),( Yong Han Paik ),( Michael Haimer ),( Kojiro Taura ),( Yuzo Kodama ),( Claude Sirlin ),( Elizabeth Yu ),( Ruth T Yu ),( Michael Downes ),( Ronald M Evans ),( David A Brenner ),( Be 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

        Background: Peroxisome Proliferator-Activated Receptor delta (PPAR), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle and liver. The aim of our study was to assess the effect of a new and highly selective PPAR agonist KD3010 in experimental mouse models of liver fibrosis induced by carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Methods: Male adult C57/B6 mice were treated daily with vehicle or KD3010 by oral gavage. Liver fibrosis was induced by repeated intraperitoneal injections of CCl4 or BDL. For in vitro study, primary hepatocytes were isolated and incubated with/without KD3010. Results: PPAR agonist KD3010 ameliorates liver injury induced by CCl4 injections. Deposition of extracellular matrix proteins was lower in the KD3010 group as compared to the control group. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using BDL for three weeks. Primary hepatocytes incubated with KD3010 were protected from serum starvation or CCl4-induced cell death, in part due to reduced reactive oxygen species (ROS) production. Conclusions: The PPAR agonist KD3010 has hepatoprotective and antifibrotic effects in animal models of liver fibrosis suggesting a new mechanistic and therapeutic approach in treating patients with chronic liver diseases.

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