Effect of arsenic trioxide on bleomycin-induced pulmonary fibrosis in rats

AIM:To observe the effect of arsenic trioxide (ATO) on bleomycin-induced pulmonary fibrosis in rats. METHODS:Pulmonary fibrosis was induced in Sprague-Dawley (SD) rats by intratracheal instillation of bleomycin (BLM). The rats in ATO treatment group,steroid treatment group and model group were intraperitoneally injected with ATO,dexamethasone or normal saline (NS),respectively,while the control rats received NS both intratracheally and intraperitoneally. The effects of ATO were evaluated by analyzing the median survival time,hydroxyproline level in the lung,semiquantitative grading of alveolitis and pulmonary fibrosis,and quantitative analysis of the collagen in lung tissue (Masson's trichrome staining). Apoptosis index (AI) of the lung was detected by using the terminal transferase dUTP-digoxygenin nick endlabeling (TUNEL) method. The results of immunohistochemical staining for some cytokines were quantitatively analyzed. RESULTS:ATO (1) prolonged the median survival time of rats with BLM-induced pulmonary fibrosis at some extent; (2) attenuated the alveolitis and pulmonary fibrosis,reduced hydroxyproline level and collagen deposition in the lung tissue; (3) increased the AI of lung tissue at a certain phase; and decreased the levels of transforming growth factor-β1(TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1),increased the content of in-terferon-γ (IFN-γ),but did not influence the concentration of matrix metalloproteinase-9 (MMP-9) significantly. CONCLUSION:ATO might attenuate BLM-induced pulmonary fibrosis in rats via increasing the AI in the lung tissue.