title: Dipyridamole attenuates ischemia reperfusion induced acute kidney injury through adenosinergic A1 and A2A receptor agonism in rats.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Nikkita
authors.initials: N
authors.lastname: Puri
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Vinita
authors.initials: V
authors.lastname: Mohey
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Manjinder
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.|Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India.
authors.forename: Tajpreet
authors.initials: T
authors.lastname: Kaur
authors.affiliation: Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India.
authors.forename: Devendra
authors.initials: D
authors.lastname: Pathak
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.|Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Harpal Singh
authors.initials: HS
authors.lastname: Buttar
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India. apsingh82@gmail.com.
authors.forename: Amrit Pal
authors.initials: AP
authors.lastname: Singh
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002110:Caffeine / Q000494:pharmacology; D019610:Cytoprotection; D004176:Dipyridamole / Q000494:pharmacology*; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D015415:Biomarkers; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D002110:Caffeine; D004176:Dipyridamole
keywords: Adenosine; Dipyridamole; Ischemia; Kidney; Oxidative stress