Taner İrem, Bal Nur Banu, Dizakar Saadet Özen Akarca, Bay Veysel, Demirel Mürşide Ayşe
Gazi University Health Research and Application Center, Gazi Hospital, Ankara, Türkiye.
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye.
Inflammopharmacology. 2025 Sep 1. doi: 10.1007/s10787-025-01918-4.
Ulcerative colitis is a chronic inflammatory disease affecting the gastrointestinal tract. In addition to treatments aimed at healing inflammation and tissue damage, addressing redox imbalance and mitochondrial dysfunction is crucial. The aim of the present study is to investigate the effects of Alpha-Lipoic Acid (ALA), either alone or in combination with mesalamine, on oxidative/nitrosative stress, mitochondrial dynamics, and histopathological changes in a rat model of ulcerative colitis. Rats were divided into Control (C), Ulcerative Colitis (UC), Mesalamine (M), ALA, and Mesalamine + Alpha-lipoic acid (M + ALA) groups. Colitis was induced by intrarectal administration of 4% acetic acid. The disease activity index was the highest in the UC group and the lowest in the M + ALA group among the treatment groups. Macroscopic scores in the UC, M, and ALA groups were significantly higher compared to the C group. The oxidative stress index was the highest in the UC group, with significantly elevated levels compared to the C, ALA, and M + ALA groups. The nitrotyrosine level was also highest in the UC group and significantly elevated compared to the C, M, ALA, and M + ALA groups. Dynamin-related protein 1, Mitofusin-2, and PTEN-induced putative kinase 1 proteins showed significant increases in the UC group compared to the C group. In contrast, these protein levels were significantly reduced in the M + ALA group compared to the UC group. Histopathological scoring in the UC group increased, and ALA administration significantly ameliorated these parameters. Our results indicate that ALA has beneficial effects on increased oxidative stress, impaired mitochondrial dynamics, and altered histopathological scores in the rat colitis model.
溃疡性结肠炎是一种影响胃肠道的慢性炎症性疾病。除了旨在治愈炎症和组织损伤的治疗方法外，解决氧化还原失衡和线粒体功能障碍至关重要。本研究的目的是研究α-硫辛酸（ALA）单独或与美沙拉嗪联合使用对溃疡性结肠炎大鼠模型的氧化/亚硝化应激、线粒体动力学和组织病理学变化的影响。将大鼠分为对照组（C）、溃疡性结肠炎组（UC）、美沙拉嗪组（M）、ALA组和美沙拉嗪+α-硫辛酸组（M+ALA）。通过直肠内注射4%乙酸诱导结肠炎。在各治疗组中，疾病活动指数在UC组中最高，在M+ALA组中最低。与C组相比，UC组、M组和ALA组的宏观评分显著更高。氧化应激指数在UC组中最高，与C组、ALA组和M+ALA组相比显著升高。硝基酪氨酸水平在UC组中也最高，与C组、M组、ALA组和M+ALA组相比显著升高。与C组相比，动力相关蛋白1、线粒体融合蛋白2和PTEN诱导的假定激酶1蛋白在UC组中显著增加。相反，与UC组相比，这些蛋白水平在M+ALA组中显著降低。UC组的组织病理学评分增加，而ALA给药显著改善了这些参数。我们的结果表明，ALA对大鼠结肠炎模型中氧化应激增加、线粒体动力学受损和组织病理学评分改变具有有益作用。
