Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection

Autor(es)

Gois, Pedro H. F. ; Canale, Daniele ; Volpini, Rildo A. ; Ferreira, Daniela ; Veras, Mariana M. ; Andrade-Oliveira, Vinicius ; Camara, Niels O. S. ; Shimizu, Maria H. M. ; Seguro, Antonio C.

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Biology and Medicine; v. 101, p. 176-189, DEC 2016.
• Citações Web of Science: 11

Resumo

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. Methods: Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300 mg/L of drinking water, 7 days); glycerol (50%, 5 ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50 mg/ Kg, IV, 30 min after glycerol injection) + glycerol. 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(2a) (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. 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. (AU)

• Processo FAPESP: 15/11933-3 - Efeitos antioxidante e renoprotetor do alopurinol na rabdomiólise induzida por glicerol, estatina, veneno botrópico e leptospirose
• Beneficiário: Antonio Carlos Seguro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/25567-6 - Efeitos do alopurinol na injúria renal aguda induzida por glicerol
• Beneficiário: Pedro Henrique França Gois
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado