Attenuation of bleomycin induced lung fibrosis by erdosteine and inhibition of the inducible nitric oxide synthase.

BACKGROUND AND OBJECTIVES: Despite advances in treatment modalities, the discovery of optimal medical therapies still remains a necessity in the management of pulmonary fibrosis. MATERIAL AND METHODS: The experiments were performed in 35 adult Sprague Dawley rats, randomly allotted into one of five groups (n=7). The control group was treated with 1 ml/kg, 0.9 % saline; the BLM group was given a single dose of BLM (2.5 U/kg); the BLM+ER group was treated with ER (10 mg/kg/day po) for 14 days after BLM administration; the BLM+SMT group was treated with i.p injections of SMT (20 mg/kg/ day) for 14 days after BLM administration; the BLM+ER+SMT group was treated with ER and SMT for 14 days after BLM administration. At the end of day 14, the results of histopathological, biochemical, and immunohistochemical investigations were analyzed. RESULTS: Serum TNF-α, nitrate/nitrite, and TBARS levels significantly increased in BLM group compared to control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Lung tissue content of IL-6 was found to be lower in BLM+ER, BLM+SMT and BLM+ER+SMT groups compared to BLM group by immunhistochemical examinations (p < 0.01, p < 0.01 and p < 0.001, respectively). Similarly, the TNF-α reactions (p < 0.01 for each group) and NF-kB expressions were shown to be significantly different among the study groups (p < 0.05, p < 0.05 and p < 0.001, respectively). CONCLUSION: Based on our study, ER and SMT attenuate BLM-induced pulmonary fibrosis; the combination of two agents has a greater protective efficacy against fibrosis than one alone, reducing the inflammatory markers (Tab. 2, Fig. 2, Ref. 31).