Puri Nikkita, Mohey Vinita, Singh Manjinder, Kaur Tajpreet, Pathak Devendra, Buttar Harpal Singh, Singh Amrit Pal
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India.
Naunyn Schmiedebergs Arch Pharmacol. 2016 Apr;389(4):361-8. doi: 10.1007/s00210-015-1206-2. Epub 2016 Jan 4.
Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30 mg/kg, intraperitoneal, i.p.) was administered 30 min before subjecting the rats to renal IRI. In separate groups, caffeine (50 mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.
双嘧达莫（DYP）是一种具有显著血管舒张、抗氧化和抗炎活性的抗血小板药物。本研究调查了腺苷受体在DYP介导的对大鼠缺血再灌注诱导的急性肾损伤（AKI）的保护作用中的作用。大鼠双侧肾脏缺血40分钟，随后再灌注24小时。通过测量大鼠的肌酐清除率、血尿素氮、尿酸、血钾、钠分数排泄和微量蛋白尿来评估缺血再灌注损伤（IRI）诱导的肾损伤。通过定量硫代巴比妥酸反应性物质、超氧阴离子生成和还原型谷胱甘肽水平来评估肾组织中的氧化应激。进行苏木精-伊红染色以观察肾组织的组织病理学变化。在大鼠接受肾脏IRI前30分钟腹腔注射DYP（10和30mg/kg）。在单独的组中，在大鼠接受肾脏IRI前，将咖啡因（50mg/kg，腹腔注射），一种腺苷能A1和A2A受体拮抗剂，与DYP治疗一起或不与DYP治疗一起给药。血清和尿液参数的显著变化、氧化应激增强以及肾组织的组织病理学变化证明了缺血再灌注诱导的AKI。DYP的给药显示出对AKI的保护作用。预先用咖啡因治疗消除了DYP介导的肾保护作用，表明A1和A2A腺苷受体在DYP介导的大鼠肾保护作用中起作用。得出结论，腺苷受体在DYP介导的对缺血再灌注诱导的AKI的抗氧化和肾保护作用中起明确作用。
