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Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.
- Source :
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Free radical biology & medicine [Free Radic Biol Med] 2016 Dec; Vol. 101, pp. 176-189. Date of Electronic Publication: 2016 Oct 18. - Publication Year :
- 2016
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Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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-PGF <subscript>2a</subscript> (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.<br />Conclusions: 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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Acute Kidney Injury chemically induced
Acute Kidney Injury complications
Acute Kidney Injury pathology
Animals
Apoptosis drug effects
Dinoprost antagonists & inhibitors
Dinoprost biosynthesis
Epithelial Cells drug effects
Epithelial Cells metabolism
Epithelial Cells pathology
Glycerol
Kidney Tubules drug effects
Kidney Tubules metabolism
Kidney Tubules pathology
Male
Muscle Cells drug effects
Muscle Cells metabolism
Muscle Cells pathology
Muscle, Skeletal drug effects
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Oxidation-Reduction
Oxidative Stress drug effects
Rats
Rats, Wistar
Reactive Oxygen Species metabolism
Rhabdomyolysis chemically induced
Rhabdomyolysis complications
Rhabdomyolysis pathology
Acute Kidney Injury prevention & control
Allopurinol pharmacology
Dinoprost analogs & derivatives
Free Radical Scavengers pharmacology
Reactive Oxygen Species antagonists & inhibitors
Rhabdomyolysis prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 101
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27769920
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2016.10.012