Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Biomed Pharmacother. 2018 May;101:188-194. doi: 10.1016/j.biopha.2018.02.070. Epub 2018 Feb 24.
Little is known about the role of tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and inducible nitric oxide synthase (iNOS) in the gastric ulcer and the effect of alpha lipoic acid (ALA) in their modulation. Hence, this experimental study was designed to assess the possible protective effect of ALA against indomethacin (IND)-induced gastric ulcer in rats, as well as to determine the possible underlying mechanisms with a special focus on TNF-α, PAI-1, and iNOS. Adult male rats (n = 28) were divided into four equal groups: the control group received distilled water, the vehicle group received 0.5% carboxymethylcellulose, the ulcer group received a single oral dose of IND (50 mg/kg) and the ALA-treated group received ALA (100 mg/kg) orally for 3 days before ulcer induction. Four hours after IND administration, all rats were sacrificed. The ulcer index, and gastric tissue homogenate contents of total antioxidant capacity (TAC), malondialdehyde (MDA), TNF-α, and PAI-1 were evaluated. Immunohistochemical evaluation of iNOS protein expression and histopathological examination of gastric tissue were investigated. The results revealed that ALA pretreatment significantly decreased the ulcer index, the gastric levels of MDA, TNF-α, PAI-1, and iNOS protein expression while increased the gastric levels of TAC as well as improved the histopathological appearance of gastric tissues. In conclusion, ALA ameliorated the IND-induced gastric ulceration. This could be attributed to its antioxidant and anti-inflammatory activities via suppression of TNF-α-induced elevation of both PAI-1 level and iNOS expression in the gastric tissue.
关于肿瘤坏死因子-α（TNF-α）、纤溶酶原激活物抑制剂-1（PAI-1）和诱导型一氧化氮合酶（iNOS）在胃溃疡中的作用以及α-硫辛酸（ALA）对它们的调节作用知之甚少。因此，本实验研究旨在评估 ALA 对吲哚美辛（IND）诱导的大鼠胃溃疡的可能保护作用，并确定可能的潜在机制，特别关注 TNF-α、PAI-1 和 iNOS。将成年雄性大鼠（n=28）分为四组：对照组给予蒸馏水，载体组给予 0.5%羧甲基纤维素，溃疡组给予单次口服 IND（50mg/kg），ALA 处理组给予 ALA（100mg/kg）口服，在诱导溃疡前 3 天。IND 给药后 4 小时，所有大鼠均被处死。评估溃疡指数和胃组织匀浆中总抗氧化能力（TAC）、丙二醛（MDA）、TNF-α和 PAI-1 的含量。还研究了 iNOS 蛋白表达的免疫组织化学评价和胃组织的组织病理学检查。结果表明，ALA 预处理可显著降低溃疡指数、胃 MDA、TNF-α、PAI-1 和 iNOS 蛋白表达水平，同时增加胃 TAC 水平并改善胃组织的组织病理学表现。结论：ALA 可改善 IND 诱导的胃溃疡。这可能归因于其抗氧化和抗炎活性，通过抑制 TNF-α 诱导的 PAI-1 水平和 iNOS 表达升高。
