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Pioglitazone Prevents Early-Phase Hepatic Fibrogenesis Caused by Carbon Tetrachloride

https://doi.org/10.1006/bbrc.2002.6385Get rights and content

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 (CCl4) administration in the rat. Pioglitazone (1 mg/kg BW) prevented pericentral fibrosis and induction of α-smooth muscle actin (SMA) 72 h after CCl4 administration (1 ml/kg BW). CCl4 induction of α1(I)procollagen mRNA in the liver was blunted by pioglitazone to the levels almost 2/3 of CCl4 alone. Pioglitazone also prevented CCl4-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 CCl4.

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This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Technology, and Culture of Japan.

1

M.Y. is a member of the staff of Division of Biochemistry, Central Laboratory for Medical Science, Juntendo University School of Medicine.

2

To whom correspondence and reprint requests should be addressed. Fax: +81-3-3813-8862. E-mail: [email protected].

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