AbdelGhany Morsy Suzan Awad, Abd El Mottelib Lobna M M A, Assem Sara, Abd El Aziz M M, Elgeziry Anne H
Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt.
Pathological Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, 21461, Jeddah, Saudi Arabia.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 16. doi: 10.1007/s00210-025-04109-8.
Ulcerative colitis (UC) is one of the inflammatory bowel diseases characterized by colonic damage. Epigenetic mechanisms are suggested to play a role in the pathogenesis of UC. Pioglitazone has shown promise for the treatment of UC; however, the role of epigenetic pathways in this effect is unclear. The current study aimed to explore the therapeutic and protective effects of pioglitazone against acetic acid-induced colitis (AA-C) in rats and the role of epigenetic modulation and antioxidant mechanisms in this effect. Forty male albino rats were divided into four groups (n = 10/group): control (normal saline), acetic-acid-induced ulcerative colitis (AA-C) (3 days, 2 ml acetic acid 4%), pioglitazone-treated (AA, followed by 3-week oral pioglitazone 25 mg/kg/day), and pioglitazone-protected groups (3-day oral pioglitazone 25 mg/kg/day before AA, continued with AA, and 3 weeks later). After the experiment, the body weight, colon weight-to-length ratio, and colonic tissue were evaluated. The colonic expression of epigenetic markers (DNA methyltransferase- 1 and methylated E-cadherin), oxidative stress marker (malondialdehyde), antioxidant enzyme (superoxide dismutase), and angiotensin-converting enzyme- 2 (ACE- 2) was evaluated. The pioglitazone-protected and treated groups showed significant inhibition of DNA methyltransferase- 1 and methylated E-cadherin with improvement in colonic tissue macroscopic and microscopic signs of inflammation, improved weight, less oxidative stress, and less ACE- 2 expression. These beneficial actions were more pronounced among the pioglitazone-protected group. Pioglitazone could mitigate AA-C in rats by inhibiting epigenetic DNA methyltransferase- 1 and E-cadherin gene methylation. It also inhibits oxidative stress and prevents the overexpression of ACE- 2.
溃疡性结肠炎（UC）是一种以结肠损伤为特征的炎症性肠病。表观遗传机制被认为在UC的发病机制中起作用。吡格列酮已显示出治疗UC的潜力；然而，表观遗传途径在这种作用中的作用尚不清楚。本研究旨在探讨吡格列酮对大鼠乙酸诱导的结肠炎（AA-C）的治疗和保护作用，以及表观遗传调节和抗氧化机制在这种作用中的作用。将40只雄性白化大鼠分为四组（每组n = 10）：对照组（生理盐水）、乙酸诱导的溃疡性结肠炎组（AA-C）（3天，2 ml 4%乙酸）、吡格列酮治疗组（AA后，口服吡格列酮25 mg/kg/天，持续3周）和吡格列酮保护组（AA前口服吡格列酮25 mg/kg/天，持续3天，随后进行AA诱导，并持续3周）。实验结束后，评估体重、结肠重量与长度比以及结肠组织。评估结肠中表观遗传标记物（DNA甲基转移酶-1和甲基化E-钙黏蛋白）、氧化应激标记物（丙二醛）、抗氧化酶（超氧化物歧化酶）和血管紧张素转换酶-2（ACE-2）的表达。吡格列酮保护组和治疗组显示DNA甲基转移酶-1和甲基化E-钙黏蛋白受到显著抑制，结肠组织的宏观和微观炎症体征得到改善，体重增加，氧化应激减轻，ACE-2表达减少。这些有益作用在吡格列酮保护组中更为明显。吡格列酮可通过抑制表观遗传DNA甲基转移酶-1和E-钙黏蛋白基因甲基化来减轻大鼠的AA-C。它还抑制氧化应激并防止ACE-2的过度表达。
