Iraz Mustafa, Erdogan Hasan, Kotuk Mahir, Yağmurca Murat, Kilic Talat, Ermis Hilal, Fadillioğlu Ersin, Yildirim Zeki
Inonu University, Medical Faculty, Department of Pharmacology, 44069 Malatya, Turkey.
Pharmacol Res. 2006 Mar;53(3):310-6. doi: 10.1016/j.phrs.2005.12.009. Epub 2006 Feb 3.
Oxidative stress has been implicated in the pathogenesis of bleomycin-induced lung fibrosis and many antioxidant agents have been studied for prevention and treatment of the disease in animals and humans. We therefore examined whether Ginkgo biloba (Gb), a flavonoid-rich antioxidant, inhibits bleomycin-induced lung fibrosis in rats. Male Sprague-Dawley rats were given a single dose of bleomycin (2.5 mg/kg, intratracheally) in pulmonary fibrosis groups and saline in controls. First dose of Gb was given a day before the bleomycin injection and continued until sacrifice. At day 14, fibrotic changes in lung were estimated to occur by Aschoft's criteria and lung hydroxyproline content. Bleomycin challenge provoked severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and typical histological findings, which is prevented by Gb. Hydroxyproline level was significantly higher (13.51+/-0.87 mg/g dried tissue) in bleomycin treated rats than controls (9.2+/-1.33), and its level was remained to the control levels (7.38+/-0.76) in rats treated with prophylactic Gb. On the other hand, bleomycin injection significantly reduced activities of glutathione peroxidase, superoxide dismutase and catalase in lung tissue which is prevented by Gb. Also, bleomycin injection resulted in a marked increase of malondialdehyde and nitrite level which is attenuated by Gb. The data suggest that Gb has a potent antioxidant activity in the model of bleomycin-induced lung fibrosis in rats, and therefore has a potent antifibrotic activity against bleomycin-induced lung fibrosis model in rats.
氧化应激与博来霉素诱导的肺纤维化发病机制有关,许多抗氧化剂已在动物和人类中进行了预防和治疗该疾病的研究。因此,我们研究了富含黄酮类抗氧化剂的银杏(Gb)是否能抑制大鼠博来霉素诱导的肺纤维化。将雄性Sprague-Dawley大鼠分为肺纤维化组和对照组,肺纤维化组经气管内给予单剂量博来霉素(2.5mg/kg),对照组给予生理盐水。在博来霉素注射前一天给予第一剂Gb,并持续至处死。在第14天,根据Aschoft标准和肺羟脯氨酸含量评估肺内纤维化变化。博来霉素激发了严重的肺纤维化,肺组织羟脯氨酸含量显著增加并出现典型的组织学表现,而Gb可预防这种情况。博来霉素处理的大鼠羟脯氨酸水平(13.51±0.87mg/g干组织)显著高于对照组(9.2±1.33),而预防性给予Gb的大鼠其水平恢复至对照水平(7.38±0.76)。另一方面,博来霉素注射显著降低了肺组织中谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶的活性,而Gb可预防这种情况。此外,博来霉素注射导致丙二醛和亚硝酸盐水平显著升高,而Gb可使其降低。数据表明,Gb在大鼠博来霉素诱导的肺纤维化模型中具有强大的抗氧化活性,因此对大鼠博来霉素诱导的肺纤维化模型具有强大的抗纤维化活性。