Protective Effect of Ambroxol against Paraquat-induced Pulmonary Fibrosis in Rats

OBJECTIVE: To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat. METHODS: Adult male Sprague-Dawley rats (n=144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-β1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed. RESULTS: In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis. CONCLUSION: The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.