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

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.