title: Acute pretreatment with chloroquine attenuates renal I/R injury in rats.
abstract: BACKGROUND
  Acute kidney injury (AKI) still remains an unresolved problem in pharmacotherapy and renal inflammation is a major factor in its development. Chloroquine, a well-known antimalarial drug, posses pleitropic effects as well: antiinflammatory, anticoagulant and vascular actions. The effects of chloroquine on renal function may involve significant increase in urine flow rate, glomerular filtration rate and sodium excretion, as well as stimulation of nitric oxide synthase. However, its role in experimental models of renal I/R injury is unknown. We aimed to analyze the acute effects of a single-dose intravenous chloroquine administered at three different times in the experimental model of I/R injury in rat.
  
  
  METHODS
  Rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion with saline lasting 4 hours. Chloroquine was administered in doses of 0.3 mg/kg i.v. and 3 mg/kg i.v. 30 min before ischemia, 30 min before reperfusion and 5 min before reperfusion. Selected a hemodynamic, biochemical and morphological parameters were followed in the Sham-operated animals and rats subjected to I/R injury and pretreated with saline or chloroquine.
  
  
  RESULTS
  Chloroquine (0.3 and 3 mg/kg, i.v.) protected the I/R injured kidney in an U-shaped manner. Both doses were protective regarding biochemical and histological markers of the I/R injury (serum urea, creatinine and fractional excretion of sodium, as well as total histological score, tubular necrosis score and KIM-1 staining score) (P<0.05 vs. corresponding controls, i.e. rats subjected to I/R injury and treated with saline only). The protective effects of the lower dose of chloroquine were more profound. Time-related differences between pretreatments were not observed (P>0.05, all).
  
  
  CONCLUSIONS
  Our study shows for the first time that a single dose of chloroquine (0.3 mg/kg i.v.) could afford significant protection of the injured rat kidney.
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Todorovic
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Medic
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Basta-Jovanovic
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Radojevic Skodric
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Radan
authors.initials: R
authors.lastname: Stojanovic
authors.affiliation: Department of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Branislav
authors.initials: B
authors.lastname: Rovcanin
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D002738:Chloroquine / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D002738:Chloroquine; D014508:Urea; D012964:Sodium; D003404:Creatinine; D019001:Nitric Oxide Synthase