AIM: To observe the role of endogenous peroxynitrite (ONOO-) in pulmonary injury and fibrosis induced by bleomycin A5 (BLM-A5) in rats. METHODS: Pulmonary injury and fibrosis of rats were evaluated by testing the level of lipid peroxides (LPO) in out-going pulmonary blood (OPB), and by observing histological changes, including type III and type I collagen changes in lung which were examined with Sirius red staining under polarized light. The peroxynitrite expression was detected by immunohistochemistry for nitrotyrosine (NT), a marker of the peroxynitrite production. RESULTS: (1) The level of LPO was elevated in OPB of rats on d 14 after intratracheal administration of BLM-A5. Thickened alveolar wall and macrophage infiltration were seen, and fibroblasts were near by the interstitial macrophages. Increased amounts of type III collagen and type I collagen were deposited in disoriented fashion. (2) High expression of ONOO- was detected in alveolar epithelial cells and pulmonary interstitial macrophages. (3) The above changes were reduced by aminoguanidine (AG), an inhibitor of nitric oxide synthase (iNOS). CONCLUSION: Endogenous ONOO- mediated BLM-A5-induced pulmonary toxicity. The therapeutic potential of AG for pulmonary injury and fibrosis was realized partly by reducing ONOO- formation.
AIM: To observe the role of endogenous peroxynitrite (ONOO-) in pulmonary injury and fibrosis induced by bleomycin A5 (BLM-A5) in rats. METHODS:Pulmonary injury and fibrosis of rats were evaluated by testing the level of lipid peroxides (LPO) in out-going pulmonary blood (OPB), and by observing histological changes, including type III and type I collagen changes in lung which were examined with Sirius red staining under polarized light. The peroxynitrite expression was detected by immunohistochemistry for nitrotyrosine (NT), a marker of the peroxynitrite production. RESULTS: (1) The level of LPO was elevated in OPB of rats on d 14 after intratracheal administration of BLM-A5. Thickened alveolar wall and macrophage infiltration were seen, and fibroblasts were near by the interstitial macrophages. Increased amounts of type III collagen and type I collagen were deposited in disoriented fashion. (2) High expression of ONOO- was detected in alveolar epithelial cells and pulmonary interstitial macrophages. (3) The above changes were reduced by aminoguanidine (AG), an inhibitor of nitric oxide synthase (iNOS). CONCLUSION: Endogenous ONOO- mediated BLM-A5-induced pulmonary toxicity. The therapeutic potential of AG for pulmonary injury and fibrosis was realized partly by reducing ONOO- formation.
Authors: Anand Krishnan V Iyer; Vani Ramesh; Carlos A Castro; Vivek Kaushik; Yogesh M Kulkarni; Clayton A Wright; Rajkumar Venkatadri; Yon Rojanasakul; Neelam Azad Journal: J Cell Biochem Date: 2015-11 Impact factor: 4.429
Authors: Aastha Arora; Vikas Bhuria; Puja P Hazari; Uma Pathak; Sweta Mathur; Bal G Roy; Rajat Sandhir; Ravi Soni; Bilikere S Dwarakanath; Anant N Bhatt Journal: Front Pharmacol Date: 2018-04-24 Impact factor: 5.810