Department of Pharmacology, Faculty of Pharmacy, University of Alkafeel, Najaf, Iraq.
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Kufa, Iraq.
J Med Life. 2023 Apr;16(4):623-630. doi: 10.25122/jml-2022-0280.
Ischemia/reperfusion injury (IRI) is a common cause of kidney damage, characterized by oxidative stress and inflammation. In this study, we investigated the potential protective effects of IAXO-102, a chemical compound, on experimentally induced IRI in male rats. The bilateral renal IRI model was used, with 24 adult male rats randomly divided into four groups (N=6): sham group (laparotomy without IRI induction), control group (laparotomy plus bilateral IRI for 30 minutes followed by 2 hours of reperfusion), vehicle group (same as control but pre-injected with the vehicle), and treatment group (similar to control but pre-injected with IAXO-102). We measured several biomarkers involved in IRI pathophysiology using enzyme-linked immunosorbent assay (ELISA), including High mobility group box1 (HMGB1), nuclear factor kappa b-p65 (NF-κB p65), interleukin beta-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-isoprostane, Bcl-2 associated X protein (BAX), heat shock protein 27 (HSP27), and Bcl-2. Statistical analysis was performed using one-way ANOVA and Tukey post hoc tests. Our results showed that IAXO-102 significantly improved kidney function, reduced histological alterations, and decreased the inflammatory response (IL-1, IL-6, and TNF) caused by IRI. IAXO-102 also decreased apoptosis by reducing pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 without impacting HSP27. In conclusion, our findings suggest that IAXO-102 had a significant protective effect against IRI damage in the kidneys.
缺血再灌注损伤(IRI)是肾脏损伤的常见原因,其特征为氧化应激和炎症反应。在这项研究中,我们研究了一种名为 IAXO-102 的化合物对雄性大鼠实验性诱导的 IRI 的潜在保护作用。我们使用双侧肾脏 IRI 模型,将 24 只成年雄性大鼠随机分为四组(每组 6 只):假手术组(仅行剖腹术,不诱导 IRI)、对照组(剖腹术加双侧 IRI 30 分钟,再灌注 2 小时)、载体组(与对照组相同,但预先注射载体)和治疗组(与对照组相似,但预先注射 IAXO-102)。我们使用酶联免疫吸附测定法(ELISA)测量了几种与 IRI 病理生理学相关的生物标志物,包括高迁移率族蛋白 B1(HMGB1)、核因子 kappa B-p65(NF-κB p65)、白细胞介素 1β(IL-1β)、白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)、8-异前列腺素、Bcl-2 相关 X 蛋白(BAX)、热休克蛋白 27(HSP27)和 Bcl-2。使用单因素方差分析和 Tukey 事后检验进行统计学分析。我们的结果表明,IAXO-102 显著改善了肾功能,减轻了组织学改变,并降低了 IRI 引起的炎症反应(IL-1、IL-6 和 TNF)。IAXO-102 还通过减少促凋亡 Bax 和增加抗凋亡 Bcl-2 来减少细胞凋亡,而不影响 HSP27。总之,我们的研究结果表明,IAXO-102 对肾脏的 IRI 损伤具有显著的保护作用。