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

Abstract

Background and objectives: Despite advances in treatment modalities, the discovery of optimal medical therapies still remains a necessity in the management of pulmonary fi brosis. Material and methods:The experiments were performed in 35 adult Sprague Dawley rats, randomly allotted into one of fi ve 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 signifi cantly 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 signifi cantly 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 fi brosis; the combination of two agents has a greater protective effi cacy against fi brosis than one alone, reducing the infl ammatory markers (Tab. 2, Fig. 2, Ref. 31). Text in PDF www.elis.sk.

Pyrrolidine dithiocarbamate attenuates paraquat-induced acute pulmonary poisoning in vivo via transforming growth factor β1 and nuclear factor κB pathway interaction

“…19 Hence, recent studies have attracted attention to experimental models that show the inhibition of lung fibrosis by thiol-based antioxidants including N -acetylcysteine, carbocysteine, erdostein, and captopril. 22 –24 In this study, PDTC dramatically decreased lung hydroxyproline levels in our experimental PQ + PDTC group compared to levels observed in the PQ group. The presence of hydroxyproline is usually taken as an indication of collagen accumulation; thus, PDTC suppresses collagen accumulation.…”

Clinical aspects of the use of erdosteine in respiratory diseases

“…A. Guzel et al подтвердили роль эрдостеина как ингибитора нитрозивного стресса при заболеваниях органов дыхания и продемонстрировали, что метаболит данного препарата снижает синтез интерлейкина-6, TNF-α и NF-kB, препятствуя тем самым развитию легочного фиброза, вызванного блеомицином [59]. Эти экспериментальные данные свидетельствуют о том, что эрдостеин заслуживает дальнейшего изучения его места в терапии пациентов с прогрессирующим легочным фиброзом.…”

Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent

“…Several experimental studies have shown that erdosteine is effective in preventing bleomycin-induced lung fibrosis in rats possibly via the repression of neutrophil accumulation, inhibition of lipid peroxidation, and maintenance of antioxidant and free radical scavenger properties [ 11 , 45 , 46 ]. There is also evidence that erdosteine particularly when combined with S -methyl-isothiourea sulfate, a nitric oxide synthase inhibitor, inhibits pulmonary inflammation, decreases IL-6, TNF-α and NF-kB production, and attenuates bleomycin-induced pulmonary fibrosis [ 47 ]. This experimental evidence suggests that erdosteine merits further investigation in patients with pulmonary fibrosis to treat this life-threatening disease with a large unmet medical need.…”