title: Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.
abstract: Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI.
  
  
  
  Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol.
  
  
  
  Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF2a(F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade.
  
  
  
  Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication.
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil. Electronic address: pedrogoismd@usp.br.
authors: Pedro H F
authors: PHF
authors: Gois
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Daniele
authors: D
authors: Canale
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Rildo A
authors: RA
authors: Volpini
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Daniela
authors: D
authors: Ferreira
authors: Laboratory of Medical Research - LIM05, Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Mariana M
authors: MM
authors: Veras
authors: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors: Vinicius
authors: V
authors: Andrade-Oliveira
authors: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors: Niels O S
authors: NOS
authors: Câmara
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Maria H M
authors: MHM
authors: Shimizu
authors: Laboratory of Medical Research - LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Antonio C
authors: AC
authors: Seguro
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005990:Glycerol; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D000493:Allopurinol; D015237:Dinoprost; D005990:Glycerol
keywords: Acute kidney injury; Allopurinol; Glycerol; Inflammasome; Oxidative stress; Rhabdomyolysis