Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats

Hou Dong Wang, Mutsuo Yamaya, Shoji Okinaga, Yuxia Jia, Masahito Kamanaka, Hidenori Takahashi, Li Ya Guo, Takashi Ohrui, Hidetada Sasaki

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Many possible treatments for pulmonary fibrosis have been investigated, but except for some current clinical trials, none have succeeded in clinical trials. On the basis of the antioxidant action of bilirubin (BIL), we examined the effects of hyperbilirubinemia on the development of bleomycin (BLM)-induced pulmonary fibrosis in rats. The animals' plasma BIL level was kept within 3 and 10 mg/dl by repeated intravenous infusion of a high dose of BIL. We studied the inhibitory effects of hyperbilirubinemia on BLM-induced pulmonary fibrosis through histopathologic and biochemical analyses. Mortality of rats with BLM-induced pulmonary fibrosis was significantly lower in the three groups with hyperbilirubinemia. The ameliorating effect of hyperbilirubinemia on pulmonary fibrosis was shown by lung histology, as well as by a decreased lung content of hydroxyproline and reduced bronchoalveolar lavage fluid (BALF) concentration of transforming growth factor (TGF)-β1. The number of polymorphonuclear leukocytes and lymphocytes in BALF was also decreased in the groups with hyperbilirubinemia. Furthermore, oxidative metabolites of BIL in urine were present at significantly higher levels in BLM-treated rats with hyperbilirubinemia than in those without hyperbilirubinemia. These data suggest that the antioxidative action of BIL can attenuate BLM-induced pulmonary fibrosis, partly by inhibiting lung inflammation and production of TGF-β1.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number3
DOIs
StatePublished - Feb 1 2002

Fingerprint

Hyperbilirubinemia
Pulmonary Fibrosis
Bleomycin
Bilirubin
Bronchoalveolar Lavage Fluid
Transforming Growth Factors
Clinical Trials
Lung
Hydroxyproline
Lymphocyte Count
Intravenous Infusions
Pneumonia
Histology
Neutrophils
Antioxidants
Urine
Mortality

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Wang, H. D., Yamaya, M., Okinaga, S., Jia, Y., Kamanaka, M., Takahashi, H., ... Sasaki, H. (2002). Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. American Journal of Respiratory and Critical Care Medicine, 165(3), 406-411. https://doi.org/10.1164/ajrccm.165.3.2003149
Wang, Hou Dong ; Yamaya, Mutsuo ; Okinaga, Shoji ; Jia, Yuxia ; Kamanaka, Masahito ; Takahashi, Hidenori ; Guo, Li Ya ; Ohrui, Takashi ; Sasaki, Hidetada. / Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. In: American Journal of Respiratory and Critical Care Medicine. 2002 ; Vol. 165, No. 3. pp. 406-411.
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Wang, HD, Yamaya, M, Okinaga, S, Jia, Y, Kamanaka, M, Takahashi, H, Guo, LY, Ohrui, T & Sasaki, H 2002, 'Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats', American Journal of Respiratory and Critical Care Medicine, vol. 165, no. 3, pp. 406-411. https://doi.org/10.1164/ajrccm.165.3.2003149

Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. / Wang, Hou Dong; Yamaya, Mutsuo; Okinaga, Shoji; Jia, Yuxia; Kamanaka, Masahito; Takahashi, Hidenori; Guo, Li Ya; Ohrui, Takashi; Sasaki, Hidetada.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 3, 01.02.2002, p. 406-411.

Research output: Contribution to journalArticle

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T1 - Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats

AU - Wang, Hou Dong

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AU - Sasaki, Hidetada

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