Abdelsameea Ahmed Ahmed, Alsemeh Amira Ebrahim, Alabassery Nadia, Samy Walaa, Fawzy Amal, Abbas Noha A T
Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
Department of Human Anatomy and Embryology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
Int Immunopharmacol. 2023 Feb;115:109621. doi: 10.1016/j.intimp.2022.109621. Epub 2022 Dec 25.
Ulcerative colitis (UC) is a global inflammatory bowel disease. This study aimed to assess the effects of icosapent ethyl on acetic acid-induced colitis in rats as well as the underlying mechanisms involved. 36 male Wister rats were equally divided into six groups: control, UC, mesalamine 100 mg/kg, icosapent 150mg/kg, icosapent 300 mg/kg, and EX527-icosapent 300 mg/kg groups. Except for control group, UC was induced by acetic acid instillation into colon. Drugs were administered once daily for one week then under thiopental anaesthesia, colons were excised. Colitis macroscopic and microscopic scores were assessed. A part of colon was homogenized for detection of malondialdehyde (MDA), inerleukin1 (IL-1β), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), phosphorylated Akt (pAkt) and caspase 3 levels. Silent information regulator 1 (SIRT1), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 (Nrf2) mRNA expressions were detected. Mallory-stained colonic sections were examined for collagen fibres detection. Immunohistochemistry of NF-κB and p53 expressionsin colonic sections were assessed. Acetic acid induced colitis with increments in MDA, IL-1β, TNF-α, and caspase 3 levels while decreased SOD, pAkt, SIRT1, HO-1, and Nrf2 with increased collagen fibres as well as NF-κB and p53. Icosapent decreased macro& microscopic colitis scores, MDA, IL-1β, TNF-α, and caspase 3 levels while increased SOD, pAkt, SIRT1, HO-1, and Nrf2 with decreased collagen fibres as well as NF-κB and p53. The effects of icosapent 300 mg/kg were similar to mesalamine. Icosapent effects were antagonized by EX527. Icosapent alleviated acetic acid-induced colitis via its anti-inflammatory, antioxidant, and anti-apoptotic effects mediated in part by SIRT1 pathway activation.
溃疡性结肠炎（UC）是一种全球性的炎症性肠病。本研究旨在评估二十碳五烯酸乙酯对大鼠乙酸诱导的结肠炎的影响及其潜在机制。36只雄性Wistar大鼠平均分为六组：对照组、UC组、美沙拉嗪100mg/kg组、二十碳五烯酸150mg/kg组、二十碳五烯酸300mg/kg组和EX527-二十碳五烯酸300mg/kg组。除对照组外，通过向结肠内注入乙酸诱导UC。每天给药一次，持续一周，然后在硫喷妥钠麻醉下切除结肠。评估结肠炎的宏观和微观评分。将一部分结肠匀浆以检测丙二醛（MDA）、白细胞介素1（IL-1β）、肿瘤坏死因子（TNF-α）、超氧化物歧化酶（SOD）、磷酸化Akt（pAkt）和半胱天冬酶3水平。检测沉默信息调节因子1（SIRT1）、血红素加氧酶1（HO-1）和核因子红细胞2（Nrf2）的mRNA表达。检查马洛里染色的结肠切片以检测胶原纤维。评估结肠切片中NF-κB和p53表达的免疫组织化学。乙酸诱导结肠炎，导致MDA、IL-1β、TNF-α和半胱天冬酶3水平升高，而SOD、pAkt、SIRT1、HO-1和Nrf2水平降低，同时胶原纤维以及NF-κB和p53增加。二十碳五烯酸降低了宏观和微观结肠炎评分、MDA、IL-1β、TNF-α和半胱天冬酶3水平，同时增加了SOD、pAkt、SIRT1、HO-1和Nrf2，减少了胶原纤维以及NF-κB和p53。二十碳五烯酸300mg/kg的效果与美沙拉嗪相似。EX527拮抗了二十碳五烯酸的作用。二十碳五烯酸通过部分由SIRT1途径激活介导其抗炎、抗氧化和抗凋亡作用，从而减轻乙酸诱导的结肠炎。
