Allopurinol administration in 5/6 renal ablation (Nx) rats: possible renoprotective effects independent of uric acid

• Grant number: 11/19576-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2011
• Effective date (End): November 30, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Clarice Kazue Fujihara
• Grantee: Orestes Foresto Neto
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In 1879, Mahomed described the association between chronic kidney disease (CKD), hypertension, and hyperuricemia. Uric acid (UA) is the end product of purine metabolism, while xanthine oxidase is the main catalyst for the synthesis of UA. Hyperuricemia is observed in 20-35% of patients with CKD, particularly those who also have hypertension and metabolic abnormalities such as dyslipidemia and insulin resistance. It is not known, however, whether this increase in the concentration of UA is a risk factor or just a biomarker of kidney and cardiovascular injury. Some researchers believe that hyperuricemia is a cause of the progression of CKD and cardiovascular disease, while others found no evidence to confirm this hypothesis. Allopurinol is a prodrug of oxypurinol, which is an inhibitor of xanthine oxidase activity. There is abundant evidence that allopurinol reduces systemic and glomerular hypertension, attenuates proteinuria and renal inflammation, prevents glomerular hypertrophy and arteriolar thickening, and also reduces the loss of function and the renal lesions associated with CKD. However, the mechanisms by which allopurinol promotes renal and cardiovascular protection remain uncertain. Since xanthine oxidase also catalyzes the production of reactive oxygen species (ROS), the interesting possibility arises that the renoprotective effect of allopurinol involves the limitation of oxidative stress. The aim of this study is to verify the hypothesis that the renoprotective effects of allopurinol are independent of its effect on the production of uric acid. For this purpose, allopurinol will be administered to rats subjected to 5/6 renal mass reduction (Nx), a well-known CKD model not associated with hyperuricemia, with the determination of renal functional and structural parameters at 30 and 60 days after renal ablation.(AU)

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)

FORESTO-NETO, ORESTES; AVILA, VICTOR FERREIRA; ALARCON ARIAS, SIMONE COSTA; FREGNAN ZAMBOM, FERNANDA FLORENCIA; TONO REMPEL, LISIENNY CAMPOLI; FAUSTINO, VIVIANE DIAS; MACHADO, FLAVIA GOMES; AVANCINI COSTA MALHEIROS, DENISE MARIA; ABENSUR, HUGO; SARAIVA CAMARA, NIELS OLSEN; et al. NLRP3 inflammasome inhibition ameliorates tubulointerstitial injury in the remnant kidney model. LABORATORY INVESTIGATION, v. 98, n. 6, p. 773-782, JUN 2018. (11/19576-4, 13/12256-0, 12/10926-5)