Sogut Sadik, Ozyurt Huseyin, Armutcu Ferah, Kart Levent, Iraz Mustafa, Akyol Omer, Ozen Suleyman, Kaplan Suleyman, Temel Ismail, Yildirim Zeki
Department of Biochemistry, Medical Faculty, Mustafa Kemal University, Hatay, Turkey.
Eur J Pharmacol. 2004 Jun 28;494(2-3):213-20. doi: 10.1016/j.ejphar.2004.04.045.
Oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis.
氧化应激在特发性肺纤维化的发病机制中起重要作用。因此，抗氧化剂厄多司坦有望对该疾病具有抑制潜力。肺纤维化组大鼠给予一剂博来霉素，对照组给予生理盐水。在博来霉素注射前2天给予第一剂口服厄多司坦（10mg/kg/天）以达到血液中的平稳水平，并持续至处死。在第14天，使用阿绍夫标准和肺羟脯氨酸含量评估纤维化变化。博来霉素使纤维化评分增加了五倍，而厄多司坦使其降低了87%（P>0.001），并且使羟脯氨酸含量增加了近两倍，而厄多司坦完全阻止了这种增加。博来霉素组中显著更高的髓过氧化物酶活性和丙二醛水平随后被厄多司坦显著减弱。这些结果表明，口服厄多司坦可能通过抑制中性粒细胞聚集和脂质过氧化来预防博来霉素注射引起的急性肺部炎症的发展，从而抑制随后的肺纤维化。
