Khodir Ahmed E, Ghoneim Hamdy A, Rahim Mona Abdel, Suddek Ghada M
a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.
Can J Physiol Pharmacol. 2014 Oct;92(10):839-47. doi: 10.1139/cjpp-2014-0191. Epub 2014 Aug 18.
This study was undertaken to examine the effects of montelukast (MNT) on lung and kidney injury in lipopolysaccharide (LPS) induced systemic inflammatory response. Rats were randomized into 5 groups (n = 8 rats/group): (i) Control; (ii) LPS treated (10 mg/kg body mass, by intraperitoneal (i.p.) injection); (iii) LPS + MNT (10 mg/kg, per oral (p.o.)); (iv) LPS + MNT (20 mg/kg, p.o); (v) LPS + dexamethasone (DEX; 1 mg/kg, i.p.). Twenty-four hours after sepsis was induced, the lung or kidney:body mass ratio and percent survival of rats were determined. Creatinine, blood urea nitrogen (BUN), albumin, total protein, and LDH activity were measured. Lung and kidney samples were taken for histological assessment and for determination of their malondialdehyde (MDA) and glutathione (GSH) contents. The expression of tumour necrosis factor α (TNF-α) in tissue was evaluated immunohistochemically. LPS significantly increased the organ:body mass ratio, serum creatinine, BUN, and LDH, and decreased serum albumin and total protein levels. MDA levels increased in lung and kidney tissues after treatment with LPS, and there was a concomitant reduction in GSH levels. Immunohistochemical staining of lung and kidney specimens from LPS-treated rats revealed high expression levels of TNF-α. MNT suppresses the release of inflammatory and oxidative stress markers. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. These results demonstrate that MNT could have lung and renoprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and (or) anti-inflammatory properties.
本研究旨在探讨孟鲁司特（MNT）对脂多糖（LPS）诱导的全身炎症反应中肺和肾损伤的影响。将大鼠随机分为5组（每组n = 8只大鼠）：（i）对照组；（ii）LPS处理组（腹腔注射（i.p.），10 mg/kg体重）；（iii）LPS + MNT组（口服（p.o.），10 mg/kg）；（iv）LPS + MNT组（口服，20 mg/kg）；（v）LPS +地塞米松（DEX；腹腔注射，1 mg/kg）。诱导脓毒症24小时后，测定大鼠的肺或肾与体重之比以及存活率。检测肌酐、血尿素氮（BUN）、白蛋白、总蛋白和乳酸脱氢酶（LDH）活性。采集肺和肾样本进行组织学评估，并测定其丙二醛（MDA）和谷胱甘肽（GSH）含量。采用免疫组织化学方法评估组织中肿瘤坏死因子α（TNF-α）的表达。LPS显著增加了器官与体重之比、血清肌酐、BUN和LDH，并降低了血清白蛋白和总蛋白水平。LPS处理后，肺和肾组织中的MDA水平升高，同时GSH水平降低。LPS处理大鼠的肺和肾标本免疫组织化学染色显示TNF-α表达水平较高。MNT可抑制炎症和氧化应激标志物的释放。此外，组织学评估表明MNT有效保留了组织形态。这些结果表明，MNT对内毒素血症期间的炎症过程可能具有肺和肾保护作用。这种作用可归因于其抗氧化和（或）抗炎特性。
