Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
School of Pharmacy and Pharmacology, MHIQ, QUM Network, Griffith University, Gold Coast, Queensland, Australia.
Pharmacology. 2019;103(5-6):315-319. doi: 10.1159/000497474. Epub 2019 Mar 14.
Cyclooxygenase (COX)-lipooxygenase (LOX) pathway plays a key role in the pathogenesis of renal ischemia/reperfusion (IR).
This study was aimed to evaluate the role of dietary phenol caffeic acid (CA), alone and in combination with selective COX-2 inhibitor celecoxib (CEL) in IR-induced acute renal failure (ARF) in rats.
Renal IR was induced by bilateral occlusion of renal pedicels for 90 min followed by reperfusion for 24 h. Rats were randomized into 4 groups: Sham, IR, CA + IR, and CA + CEL + IR, with 7 day treatment before IR. Serum creatinine (SCr), blood urea nitrogen (BUN), antioxidant enzymes, tumor necrosis factor alpha (TNF-α), and histopathological changes were evaluated in the kidney after IR.
Renal IR caused significant derangement in renal function and histology. In the IR group, an increase in lipid peroxidation and decreased antioxidant defense enzyme activity were observed. Pretreatment with CA and CA + CEL showed a significant decrease in the BUN, SCr, TNF-α, oxidative stress markers and corrected the histological changes in the kidney.
This study demonstrated the renoprotective potential of CA and combination of CA + CEL in IR-induced ARF in rats. The plausible mechanisms for the efficacy of CA could be attributed to its ability to modulate the -COX-LOX system in renal IR.
环氧化酶（COX）-脂氧合酶（LOX）途径在肾缺血/再灌注（IR）发病机制中起着关键作用。
本研究旨在评估膳食酚类咖啡酸（CA）单独及与选择性 COX-2 抑制剂塞来昔布（CEL）联合在大鼠 IR 诱导的急性肾衰竭（ARF）中的作用。
通过双侧肾蒂夹闭 90 分钟再灌注 24 小时诱导肾 IR。大鼠随机分为 4 组：假手术组、IR 组、CA+IR 组和 CA+CEL+IR 组，在 IR 前进行 7 天治疗。IR 后评估血清肌酐（SCr）、血尿素氮（BUN）、抗氧化酶、肿瘤坏死因子-α（TNF-α）和肾脏组织学变化。
肾 IR 导致肾功能和组织学明显紊乱。IR 组观察到脂质过氧化增加和抗氧化防御酶活性降低。CA 和 CA+CEL 预处理可显著降低 BUN、SCr、TNF-α、氧化应激标志物，并纠正肾脏的组织学变化。
本研究表明 CA 具有预防肾 IR 诱导的 ARF 的作用，CA+CEL 联合应用具有肾保护作用。CA 疗效的可能机制归因于其调节肾 IR 中 COX-LOX 系统的能力。
