The effects of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide synthase, on the bleomycin (BL)-induced lung fibrosis was evaluated in mice. The animals were placed into five groups: saline (SA)-instilled drinking water (SA + H2O), saline-instilled drinking water containing 0.5%AG (SA+0.5%AG), BL-instilled drinking water (BL+H2O), BL-instilled drinking water containing 0.2%AG (BL + 0.2%AG), and BL-instilled drinking water containing 0.5%AG (BL + 0.5%AG). The mice had free access to H2O or H2O containing AG and lab chow ad lib 2 days prior to intratracheal (IT) instillation of BL (0.07 U/mouse/100 μL) or an equivalent volume of sterile isotonic saline. The mice in the SA + 0.5%AG group consumed the greatest amount of AG without any ill effects than the mice in any other group. There were no differences in any of the measured biochemical determinants between the SA + H2O and SA + 0.5%AG control groups. The IT instillation of BL in the BL + H2O group caused significant increases in the lipid peroxidation, hydroxyproline content, and prolyl hydroxylase activity of lungs and influx of inflammatory cells in the broncheoalveolar lavage fluid (BALF) as compared to both control groups. The intake of aminoguanidine by mice in the BL + 0.5%AG group caused significant reductions in the BL-induced increases in all measured biochemical indices of lung fibrosis without any effects on the influx of inflammatory cells in the BALF. In fact, AG in both BL-treated groups additionally increased the total cell counts in the BALF from mice in the BL + 0.2%AG and BL + 0.5%AG groups as compared to the BL+ H2O group. Histopathological evaluation of the lungs revealed that the mice in the BL + 0.5%AG group had markedly fewer fibrotic lesions than mice in the BL + H2O group. These results demonstrate that aminoguanidine minimizes the BL-induced lung fibrosis at both the biochemical and the morphological level and support our earlier hypothesis that the production of nitric oxide plays a significant role in the pathogenesis lung fibrosis caused by BL.
- Inducible nitric oxide synthase
- Lung fibrosis
- Nitric oxide
ASJC Scopus subject areas
- Molecular Biology