Attenuation of CCl4-induced hepatic fibrosis by GdCl3 treatment or dietary glycine

C. A. Rivera, B. U. Bradford, K. J. Hunt, Y. Adachi, L. W. Schrum, D. R. Koop, E. R. Burchardt, R. A. Rippe, R. G. Thurman

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

The role of Kupffer cells in CCl4-induced fibrosis was investigated in vivo. Male Wistar rats were treated with phenobarbital and CCl4 for 9 wk, and a group of rats were injected with the Kupffer cell toxicant gadolinium chloride (GdCl3) or were fed glycine, which inactivates Kupffer cells. After CCl4 alone, the fibrosis score was 3.0 ± 0.1 and collagen protein and mRNA expression were elevated, but GdCl3 or glycine blunted these parameters. Glycine did not alter cytochrome P-450 2E1, making it unlikely that glycine affects CCl4 metabolism. Treatment with GdCl3 or glycine prevented CCl4-induced increases in transforming growth factor (TGF)-β1 protein levels and expression. CCl4 treatment increased α-smooth muscle actin staining (score 3.0 ± 0.2), whereas treatment with GdCl3 and glycine during CCl4 exposure blocked this effect (1.2 ± 0.5); there was no staining with glycine treatment. These results support previous in vitro data and demonstrate that treatment of rats with the selective Kupffer cell toxicant GdCl3 prevents stellate cell activation and the development of fibrosis.

Original languageEnglish (US)
Pages (from-to)G200-G207
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number1 44-1
DOIs
StatePublished - 2001

Keywords

  • Kupffer cells
  • Rat
  • Transforming growth factor-β
  • α-smooth muscle actin
  • α1(I) collagen

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Rivera, C. A., Bradford, B. U., Hunt, K. J., Adachi, Y., Schrum, L. W., Koop, D. R., Burchardt, E. R., Rippe, R. A., & Thurman, R. G. (2001). Attenuation of CCl4-induced hepatic fibrosis by GdCl3 treatment or dietary glycine. American Journal of Physiology - Gastrointestinal and Liver Physiology, 281(1 44-1), G200-G207. https://doi.org/10.1152/ajpgi.2001.281.1.g200