Pioglitazone Prevents Early-Phase Hepatic Fibrogenesis Caused by Carbon Tetrachloride

Abstract Here we investigated the effect of pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ ligand, on early-phase hepatic fibrogenesis in vivo caused by acute carbon tetrachloride (CCl 4 ) administration in the rat. Pioglitazone (1 mg/kg BW) prevented pericentral fibrosis and induction of α-smooth muscle actin (SMA) 72 h after CCl 4 administration (1 ml/kg BW). CCl 4 induction of α1(I)procollagen mRNA in the liver was blunted by pioglitazone to the levels almost 2/3 of CCl 4 alone. Pioglitazone also prevented CCl 4 -induced hepatic inflammation and necrosis, as well as increases in serum tumor necrosis factor-α levels. Further, pioglitazone inhibited the induction of αSMA and type I collagen in primary cultured hepatic stellate cells in a dose-dependent manner. In conclusion, pioglitazone inhibits both hepatic inflammation and activation of hepatic stellate cells, thereby ameliorating early-phase fibrogenesis in the liver following acute CCl 4 .