Effects of pirfenidone on the generation of reactive oxygen species in vitro

Shri N. Giri, Stephen Leonard, Xianglin Shi, Solomon B. Margolin, Val Vallyathan

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Pirfenidone is a newly developed antifibrotic drug that has been reported to retard the progression of pulmonary fibrosis induced by bleomycin and cyclophosphamide in animal models of lung fibrosis. The present in vitro studies using noncellular and cellular systems evaluated the antioxidant and cytotoxic properties of this drug. The Fenton reaction [Fe(II) + H2O2 → Fe(III) + OH + OH-] and the xanthine/xanthine oxidase system were used as sources of hydroxyl ('OH) and superoxide anion (O2-) radicals, respectively. Electron spin resonance spin trapping was used for free radical detection and measurement. The reaction rate of pirfenidone with 'OH was found to be 1.63 x 1010 M-1 s-1, which is comparable to several well- established antioxidants, such as ascorbate, glutathione, cysteine, azide, and lipoic acid. Compared to OH radicals, the O2 scavenging was less efficient 42.36 M-1 s-1 with pirfenidone. Pirfenidone was also effective in inhibiting zymosan-stimulated chemiluminescence. In a noncellular model of lipid peroxidation, pirfenidone inhibited crystalline silica-induced lipid peroxidation. The inhibition of crystalline silica-induced cytotoxic reactions and lipid peroxidation combined with the efficient antioxidant properties of pirfenidone indicate that this agent may express its antifibrotic effects partly through its ability to scavenge reactive oxygen species.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume18
Issue number3
StatePublished - 1999

Keywords

  • Antifibrosis
  • Antioxidants
  • Bleomycin
  • Cyclophosphamide
  • Electron spin resonance
  • Lipid peroxidation
  • Lung fibrosis
  • Pirfenidone
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'Effects of pirfenidone on the generation of reactive oxygen species in vitro'. Together they form a unique fingerprint.

Cite this