EFFECTS OF ALLOPURINOL ON GLYCEROL-INDUCED ACUTE KIDNEY INJURY IN WISTAR RATS

• Grant number: 14/25567-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2015
• End date: January 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Antonio Carlos Seguro
• Grantee: Pedro Henrique França Gois
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rhabdomyolysis syndrome is a disorder known for centuries. However, the causal association between rhabdomyolysis and acute kidney injury (AKI) was first described only during the World War II. The myoglobinuric AKI may be considered the most severe complication of rhabdomyolysis, occurring in 10-50 % of the cases. Intramuscular infusion of glycerol in animals reproduces the pathophysiology of the rhabdomyolysis-induced AKI in humans. Hence, it is possible, using animal models, to suggest the following mechanisms to explain the association between AKI and rhabdomyolysis: renal vasoconstriction; tubular obstruction by pigmentary casts; direct toxicity of heme protein by oxidative stress; inflammation; and apoptosis of renal tubular cells. Allopurinol (ALO), an uric acid lowering agent, is a xanthine oxidase (XO) inhibitor commonly used to treat gout. Due to its potential antioxidant effect, either by blocking the production of uric acid and/or by direct inhibition of XO, thus reducing the generation of oxygen free radicals, it has a large potential use in the prevention and treatment of various pathological conditions. The aim of this study is to investigate the effects of ALO, both prophylactic and therapeutic, on the renal function and the redox balance in an animal model of glycerol-induced AKI.We aim to evaluate in this study: renal function (accessed by inulin clearance, 24h after glycerol infusion), renal blood flow, mean arterial blood pressure, oxidative stress studies(Glutathione - GSH - and Malondialdehyde - MDA), renal tissue immunoblotting for proteins involved in the redox balance, apoptosis pathway (Western Blotting and imunohistochemistry studies) and renal infiltration of inflammatory cells.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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.. Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection. Free Radical Biology and Medicine, v. 101, p. 176-189, DEC 2016. (15/11933-3, 14/25567-6)

MASSOLA SHIMIZU, MARIA HELOISA; FRANCA GOIS, PEDRO HENRIQUE; VOLPINI, RILDO APARECIDO; CANALE, DANIELE; LUCHI, WEVERTON MACHADO; FROEDER, LEILA; HEILBERG, ITA PFEFERMAN; SEGURO, ANTONIO CARLOS. N-acetylcysteine protects against star fruit-induced acute kidney injury. RENAL FAILURE, v. 39, n. 1, p. 193-202, 2017. (15/11933-3, 14/25567-6)