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Updated: Aug 7, 2026
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
Inhibitory effect of aminoguanidine on bleomycin-induced pulmonary toxicity in rat
1Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China. chen_xiaoling123@sina.com.cn
Aim:
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.
Conclusion:
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.
Insights
Aminoguanidine (AG) effectively inhibited bleomycin-induced lung injury and fibrosis in rats. This protective effect is linked to reduced nitric oxide (NO) production, mitigating hyperoxidative damage and fibrotic changes.
Area of Science:
- Pulmonary Toxicology
- Pharmacology
- Fibrosis Research
Background:
- Bleomycin A5 (BLM-A5) is a chemotherapeutic agent known to induce pulmonary toxicity and fibrosis.
- Nitric oxide (NO) production and oxidative stress are implicated in the pathogenesis of BLM-A5-induced lung injury.
- Aminoguanidine (AG) is a known inhibitor of nitric oxide synthase.
Purpose of the Study:
- To investigate the potential inhibitory effect of aminoguanidine (AG) on bleomycin A5 (BLM-A5)-induced pulmonary toxicity in a rat model.
- To assess the impact of AG on key biomarkers of lung injury, fibrosis, and nitric oxide production following BLM-A5 administration.
Main Methods:
- Rats were intratracheally administered BLM-A5 to induce pulmonary toxicity.
- Hydroxyproline (fibrosis marker), nitrite/nitrate (NO marker), and malondialdehyde (oxidative stress marker) were quantified colorimetrically.
- Histological and morphometric analyses of lung tissue were performed using hematoxylin and eosin staining.
Main Results:
- BLM-A5 administration led to increased lung hydroxyproline and out-going pulmonary blood (OPB) malondialdehyde (MDA) levels, alongside histological evidence of alveolar collapse and interstitial fibrosis.
- Elevated nitrite/nitrate (NO2-/NO3-) levels were observed in alveolar macrophage culture supernatant and OPB post-BLM-A5 treatment.
- Aminoguanidine (AG) treatment significantly alleviated BLM-A5-induced increases in hydroxyproline and MDA, reduced lung histological damage, and blocked the augmentation of NO2-/NO3- in OPB.
Conclusions:
- Aminoguanidine (AG) demonstrates a significant inhibitory effect on pulmonary injury and fibrosis induced by bleomycin A5 (BLM-A5).
- The protective mechanism of AG appears to be associated with the suppression of nitric oxide (NO) production in the lung.
- These findings suggest AG as a potential therapeutic agent for mitigating bleomycin-induced lung damage.
