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


CONCLUSIONS
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.
Chen
Xiao-Ling
XL
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China. chen_xiaoling123@sina.com.cn
Li
Wen-Bin
WB
Zhou
Ai-Min
AM
Ai
Jie
J
Huang
Shan-Sheng
SS
D000818:Animals; D001761:Bleomycin / Q000031:analogs & derivatives*; D003094:Collagen / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000096:biosynthesis / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D001761:Bleomycin; D030421:Peroxynitrous Acid; D008315:Malondialdehyde; C025703:bleomycetin; D003094:Collagen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine