title: Evaluation of l-arginine on kidney function and vascular reactivity following ischemic injury in rats: protective effects and potential interactions.
abstract: BACKGROUND
  There is an interaction between many cell types involved in the pathophysiology of ischemic acute renal failure. Nitric oxide (NO) precursors, especially l-arginine, may have protective effects on tissue ischemia/reperfusion injury (IRI); however, their molecular mechanisms are unclear. In the present study, the interaction between l-arginine, cyclo-oxygenase (COX)-2 and reactive oxygen species (ROS) in the pathogenesis of ischemic acute renal failure was investigated.
  
  
  METHODS
  Ischemia/reperfusion injury model in rats was used and various biochemical parameters examined. The rat isolated aortic rings served as model for hypoxia/reoxygenation where endothelium dependent and independent relaxations were exerted.
  
  
  RESULTS
  Pre-treatment of rats subjected to IRI with l-arginine (125mg/kg) significantly reduced kidney MDA levels, elevated kidney SOD activity, GSH level and total NO levels at 24 and 48h after reperfusion. Kidney COX-2 level was only different in the l-arginine-treated group 48h after reperfusion compared to the IRI group. Pre-treatment with l-arginine (10(-2)M) alone or in combination with celecoxib significantly potentiated the acetylcholine (Ach)-induced relaxations in control and hypoxic rings. The effect of the combination was synergistic only in hypoxic rings. Addition of ascorbic acid to the celecoxib-arginine combination did not produce further potentiation. Sodium nitroprusside-induced relaxations in control and hypoxic rings were potentiated by l-arginine or celecoxib-arginine combination but not by ascorbic acid.
  
  
  CONCLUSIONS
  The protective effect of l-arginine may result from the interaction between NO and ROS and increased NO bioavailability. The protective effects of combined celecoxib and l-arginine against IRI could be attributed to their antioxidant activity which exceeded that of ascorbic acid.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address: senbelamira@alexpharmacy.edu.eg.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Senbel
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Amal G
authors.initials: AG
authors.lastname: Omar
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt.
authors.forename: Lobna M
authors.initials: LM
authors.lastname: Abdel-Moneim
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Hosny F
authors.initials: HF
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Tahia T
authors.initials: TT
authors.lastname: Daabees
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001011:Aorta / Q000503:physiopathology; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000068579:Celecoxib / Q000008:administration & dosage / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004357:Drug Synergism; D007677:Kidney Function Tests; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D000109:Acetylcholine; D001205:Ascorbic Acid
keywords: COX-2; Nitric oxide; Oxidative stress; Renal ischemia/reperfusion injury; l-Arginine