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Publication : Superiority of systemic bleomycin to intradermal HOCl for the study of interstitial lung disease.

First Author  Morozan A Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  20577
PubMed ID  37996447 Mgi Jnum  J:355298
Mgi Id  MGI:7560915 Doi  10.1038/s41598-023-47083-y
Citation  Morozan A, et al. (2023) Superiority of systemic bleomycin to intradermal HOCl for the study of interstitial lung disease. Sci Rep 13(1):20577
abstractText  Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and multi-organ fibrosis. Interstitial lung disease (ILD) is a complication of SSc and a leading cause of SSc-death. The administration of hypochlorous acid (HOCl) intradermally in the mouse (HOCl-SSc) purportedly shows several features typical of SSc. We studied the model by injecting BALB/c mice daily intradermally with HOCl for 6-weeks, an exposure reported to induce lung fibrosis. On day 42, the skinfold thickness and the dermal thickness were two and three times larger respectively in the HOCl group compared to controls. HOCl treatment did not result in histological features of pulmonary fibrosis nor significant changes in lung compliance. Automated image analysis of HOCl mice lungs stained with picrosirius red did not show increased collagen deposition. HOCl injections did not increase pulmonary mRNA expression of pro-fibrotic genes nor induced the production of serum advanced oxidation protein products and anti-topoisomerase 1 antibodies. Immune cells in bronchoalveolar lavage fluid (BALF) and whole lung digests were not increased in HOCl-treated animals. Since lung fibrosis is proposed to be triggered by oxidative stress, we injected HOCl to Nrf2(-/-) mice, a mouse deficient in many antioxidant proteins. Lung compliance, histology, and BALF leukocyte numbers were comparable between Nrf2(-/-) mice and wild-type controls. We conclude that the HOCl-SSc model does not manifest SSc-lung disease.
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