Al-Sadr Medical City, Al-Najaf Health Directorate, Al Najaf Al-Ashraf, Iraq.
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Kufa, Iraq.
J Med Life. 2023 Jun;16(6):925-931. doi: 10.25122/jml-2022-0309.
Renal ischemia-reperfusion injury is a critical clinical condition with a potentially fatal prognosis if not adequately managed. NHWD-870, a known Brd4 inhibitor with anti-cancer properties, exhibits additional attributes such as antioxidant, anti-inflammatory, and anti-apoptotic effects, suggesting its potential to preserve renal tissue and mitigate damage during ischemic insults. We aimed to assess the potential nephroprotective effect of NHWD-870 by investigating its anti-apoptotic, anti-inflammatory, and antioxidant properties in a rat model of renal ischemia-reperfusion injury. Male Wistar Albino rats (n=24) were randomly assigned to four groups: sham, control, vehicle, and NHWD-870. The control group experienced bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion, while the sham group underwent a laparotomy without ischemia-reperfusion induction. The vehicle group received a DMSO injection, and the NHWD-870 group was administered 3mg/kg NHWD-870 orally 24 hours before repeating the control group protocol. Blood samples were collected after reperfusion for blood urea nitrogen (BUN) and serum creatinine (SCr) analysis. ELISA method was used to assess IL-1B, BCL-2, PGF-2, and PI3K/AKT signaling pathways in renal tissue. Tubular injury severity was evaluated through histopathological analysis. NHWD-870 treatment improved renal function and histological preservation compared to the control and vehicle groups. BUN, sCR, IL-1B, BCL-2, and PGF-2 levels in renal tissue were significantly improved in the NHWD-870 group (p<0.05). Furthermore, the PI3K/AKT signaling pathway was significantly upregulated (p<0.01), and tubular injury severity was reduced in the NHWD-870 group. NHWD-870 demonstrated substantial nephroprotective effects in reducing renal damage induced by ischemia-reperfusion injury in rats. These effects may be attributed to the anti-apoptotic properties, as indicated by increased levels of the anti-apoptotic protein Bcl-2, and the reduction in oxidative stress marker PGF-2 through upregulation of the PI3K/AKT signaling pathway, along with the decrease in the inflammatory marker IL-1B.
肾缺血再灌注损伤是一种严重的临床病症，如果处理不当，可能导致致命后果。NHWD-870 是一种已知的具有抗癌特性的 Brd4 抑制剂，具有抗氧化、抗炎和抗细胞凋亡等额外特性，表明其在缺血性损伤期间具有保护肾脏组织和减轻损伤的潜力。我们旨在通过研究其在肾缺血再灌注损伤大鼠模型中的抗凋亡、抗炎和抗氧化特性来评估 NHWD-870 的潜在肾保护作用。雄性 Wistar 白化大鼠（n=24）随机分为四组：假手术组、对照组、载体组和 NHWD-870 组。对照组经历双侧肾缺血 30 分钟，然后再灌注 2 小时，而假手术组仅行剖腹术而不诱导缺血再灌注。载体组给予 DMSO 注射，NHWD-870 组在重复对照组方案前 24 小时给予 3mg/kg NHWD-870 口服。再灌注后采集血液样本用于血尿素氮（BUN）和血清肌酐（SCr）分析。ELISA 法用于评估肾组织中 IL-1B、BCL-2、PGF-2 和 PI3K/AKT 信号通路。通过组织病理学分析评估肾小管损伤严重程度。与对照组和载体组相比，NHWD-870 治疗改善了肾功能和组织保存。NHWD-870 组肾组织中 BUN、sCR、IL-1B、BCL-2 和 PGF-2 水平显著改善（p<0.05）。此外，PI3K/AKT 信号通路显著上调（p<0.01），NHWD-870 组肾小管损伤严重程度降低。NHWD-870 在减轻大鼠缺血再灌注损伤引起的肾损伤方面表现出显著的肾保护作用。这些作用可能归因于抗细胞凋亡特性，这是通过增加抗细胞凋亡蛋白 Bcl-2 的水平以及通过上调 PI3K/AKT 信号通路降低氧化应激标志物 PGF-2 来实现的，同时降低炎症标志物 IL-1B。
