Role of endogenous peroxynitrite in pulmonary injury and fibrosis induced by bleomycin A5 in rats.

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.