Pirfenidone inhibits dimethylnitrosamine-induced hepatic fibrosis in rats

Seiya Tada, Makoto Nakamuta, Munechika Enjoji, Rie Sugimoto, Hiroaki Iwamoto, Masaki Kato, Yutaka Nakashima, Hajime Nawata

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

1. In the present study, we investigated the preventive effects of pirfenidone (PFD), an antifibrotic agent, on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. 2. Treatment with DMN caused a significant decrease in bodyweight and liver weight. Oral PFD (500 mg/kg daily for 4 weeks) essentially prevented this DMN-induced loss in bodyweight and tended to suppress the loss in liver weight. There were no significant differences in liver weight and serum L-alanine aminotransferase levels between PFD-treated and -untreated groups. Pirfenidone has no major side effects in vivo. 3. Pirfenidone suppressed the induction of hepatic fibrosis determined by histological evaluation and reduced hepatic hydroxyproline levels. Expression of mRNA for type I collagen and transforming growth facter-β in the liver was also suppressed by PFD treatment. 4. Because hepatic stellate cells (HSC) are the major cellular source of extracellular matrix in hepatic fibrosis, we examined the effects of PFD on type I collagen production in vitro using rat primary HSC cultures. Pirfenidone inhibited collagen production in HSC culture in a dose-dependent manner. 5. These results demonstrate that the inhibitory effects of PFD against hepatic fibrosis may be due, at least in part, to blockade of collagen production by HSC and suggest that PFD may be potentially useful in the prevention of the development of hepatic fibrosis.

Original languageEnglish
Pages (from-to)522-527
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume28
Issue number7
DOIs
Publication statusPublished - Jul 9 2001

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Dimethylnitrosamine
Fibrosis
Liver
Hepatic Stellate Cells
Collagen Type I
Weights and Measures
Collagen
Cell Culture Techniques
pirfenidone
Hydroxyproline
Alanine Transaminase
Alanine
Extracellular Matrix

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Pirfenidone inhibits dimethylnitrosamine-induced hepatic fibrosis in rats. / Tada, Seiya; Nakamuta, Makoto; Enjoji, Munechika; Sugimoto, Rie; Iwamoto, Hiroaki; Kato, Masaki; Nakashima, Yutaka; Nawata, Hajime.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 28, No. 7, 09.07.2001, p. 522-527.

Research output: Contribution to journalArticle

Tada, S, Nakamuta, M, Enjoji, M, Sugimoto, R, Iwamoto, H, Kato, M, Nakashima, Y & Nawata, H 2001, 'Pirfenidone inhibits dimethylnitrosamine-induced hepatic fibrosis in rats', Clinical and Experimental Pharmacology and Physiology, vol. 28, no. 7, pp. 522-527. https://doi.org/10.1046/j.1440-1681.2001.03481.x
Tada, Seiya ; Nakamuta, Makoto ; Enjoji, Munechika ; Sugimoto, Rie ; Iwamoto, Hiroaki ; Kato, Masaki ; Nakashima, Yutaka ; Nawata, Hajime. / Pirfenidone inhibits dimethylnitrosamine-induced hepatic fibrosis in rats. In: Clinical and Experimental Pharmacology and Physiology. 2001 ; Vol. 28, No. 7. pp. 522-527.
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