Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation-promotion cancer model in the mouse. Academic Article uri icon

abstract

  • Liver fibrosis results from chronic tissue damage and excessive regeneration with accumulation of extracellular matrix proteins; it is a precursor of liver cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is a drug approved for idiopathic pulmonary fibrosis and this study was focused on anti-fibrotic and anti-cancer potential of pirfenidone in the liver of male B6C3F1/J mice. In a dose-finding study, mice were treated with CCl4 (0.2ml/kg ip, 2wk for 4weeks) while on a pirfenidone-containing (0-600mg/kg) diet. Pirfenidone at doses of 300 and 600mg/kg had significant anti-fibrotic (collagen) and anti-inflammatory (serum transaminases and "ballooning" hepatocyte) effects. In a sub-chronic study (14weeks), mice received CCl4 while on pirfenidone (300mg/kg) diet. Pirfenidone significantly reduced collagen deposition, but had little effect of inflammation and injury. In an initiation-promotion cancer study with N-nitrosodiethylamine and CCl4, pirfenidone (300mg/kg) did not affect incidence, size, or multiplicity of liver tumors. Overall, we conclude that while pirfenidone exhibits strong anti-fibrotic effects in early stage liver fibrosis, it is less effective in advanced liver fibrosis and was not protective in an initiation-promotion liver cancer.

published proceedings

  • Toxicol Appl Pharmacol

author list (cited authors)

  • Seniutkin, O., Furuya, S., Luo, Y., Cichocki, J. A., Fukushima, H., Kato, Y., ... Rusyn, I.

citation count

  • 19

complete list of authors

  • Seniutkin, Oleksii||Furuya, Shinji||Luo, Yu-Syuan||Cichocki, Joseph A||Fukushima, Hisataka||Kato, Yuki||Sugimoto, Hiromi||Matsumoto, Tomoko||Uehara, Takeki||Rusyn, Ivan

publication date

  • January 2018