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

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, 2×wk 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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Seniutkin O,Furuya S,Luo YS,Cichocki JA,Fukushima H,Kato Y,Sugimoto H,Matsumoto T,Uehara T,Rusyn I

doi

10.1016/j.taap.2017.11.024

subject

Has Abstract

pub_date

2018-01-15 00:00:00

pages

1-9

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(17)30469-6

journal_volume

339

pub_type

杂志文章

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