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Chronic Alcohol Ingestion Primes the Lung for Bleomycin‐Induced Fibrosis in Mice
Author(s) -
Sueblinvong Viranuj,
Kerchberger Vern E.,
Saghafi Ramin,
Mills Stephen T.,
Fan Xian,
Guidot David M.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12232
Subject(s) - bleomycin , fibrosis , lung , oxidative stress , medicine , ingestion , hydroxyproline , pulmonary fibrosis , glutathione , endocrinology , inflammation , pathology , immunology , chemistry , biochemistry , chemotherapy , enzyme
Background Alcohol abuse increases the risk for acute lung injury ( ALI ). In both experimental models and in clinical studies, chronic alcohol ingestion causes airway oxidative stress and glutathione depletion and increases the expression of transforming growth factor beta‐1 ( TGF β1), a potent inducer of fibrosis, in the lung. Therefore, we hypothesized that alcohol ingestion could promote aberrant fibrosis following experimental ALI and that treatment with the glutathione precursor s‐adenosylmethionine ( SAM e) could mitigate these effects. Methods Three‐month‐old C 57 BL /6 mice were fed standard chow ± alcohol (20% v/v) in their drinking water for 8 weeks and ± SAM e (4% w/v) during the last 4 weeks. ALI was induced by intratracheal instillation of bleomycin (2.5 units/kg), and lungs were assessed histologically at 7 and 14 days for fibrosis and at 14 days for the expression of extracellular matrix proteins and TGF β1. Results Alcohol ingestion had no apparent effect on lung inflammation at 7 days, but at 14 days after bleomycin treatment, it increased lung tissue collagen deposition, hydroxyproline content, and the release of activated TGF β1 into the airway. In contrast, SAM e supplementation completely mitigated alcohol‐induced priming of these aberrant fibrotic changes through decreased TGF β1 expression in the lung. In parallel, SAM e decreased alcohol‐induced TGF β1 and S mad3 m RNA expressions by lung fibroblasts in vitro. Conclusions These new experimental findings demonstrate that chronic alcohol ingestion renders the experimental mouse lung susceptible to fibrosis following bleomycin‐induced ALI , and that these effects are likely driven by alcohol‐mediated oxidative stress and its induction and activation of TGF β1.