Inhibitory effect of aminoguanidine on bleomycin-induced pulmonary toxicity in rat.
OBJECTIVE
To observe the inhibitory effect of aminoguanidine (AG) on the pulmonary toxicity induced by bleomycin A5 (BLM-A5) in rat.


METHODS
The contents of hydroxyproline, nitrite/nitrate (NO2-/NO3-), and malondialdehyde (MDA), which reflect fibrosis, nitric oxide (NO) production, and hyperoxidative injury of lung, were investigated by colorimetry. Histologic and morphometric examination of lung was also carried out on histological sections stained with hematoxylin and eosin (HE).


RESULTS
(1) The content of hydroxyproline in lung and MDA in out-going pulmonary blood (OPB) increased from 14 d to 30 d after intratracheal administration of BLM-A5. Collapsed alveoli and fibrotic areas were seen and a lot of fibroblasts appeared in the lung interstitum of the rats 30 d after BLM-A5. (2) The NO2-/NO3- content increased in supernatant of alveolar macrophage culture and in OPB. (3) The increment of hydroxyproline in lung and MDA in OPB induced by BLM-A5 was alleviated by aminoguanidine (AG, 20 mg.kg-1 . d-1, ip). AG also reduced the histologic and morphometric changes in lung interstitum. (4) The augment of NO2-/NO3- in OPB was blocked by AG.


CONCLUSIONS
AG had inhibitory effect on pulmonary injury and fibrosis induced by BLM-A5, and the inhibitory effect was related to the decrease of NO production in lung.
Chen
X L
XL
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China. chen_xiaoling123@sina.com.cn
Huang
S S
SS
Li
W B
WB
Wang
D H
DH
Wang
X L
XL
D000818:Animals; D001761:Bleomycin; D006146:Guanidines / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D001761:Bleomycin; D009569:Nitric Oxide; D008315:Malondialdehyde; D006909:Hydroxyproline; C004479:pimagedine