Alopurinol effect on oxidative stress and insulin resistance in individuals with Metabolic Syndrome

• Grant number: 12/03539-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2012
• Effective date (End): June 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rosa Ferreira dos Santos
• Grantee: Thales Ishizaki
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Xanthine oxidase (XO) system includes the most important enzymes involved in ROS production and it is also involved in Uric acid synthesis. Allopurinol is one of the most useful drugs in Hyperuricemia. This drug inhibits XO system, reducing plasmatic uric acid. However, Allopurinol is also useful as an oxidative stress inhibitor, even in the average plasmatic concentration of uric acid in individuals with severe myocardiopathy. It's been reported that metabolic syndrome individuals with no other associated pathologies have a higher level of oxidative stress and this mechanism leads to worse insulin resistance. The use of hypouricemic drugs like xanthine oxidase inhibitors (allopurinol) demonstrates to reduction of endothelial inflammatory markers in animal models and humans. Suggesting that allopurinol could help to improve insulin resistance, independently from their action on reducing serum uric acid. Thus, if this principle is also demonstrated to occur in humans and improvement of parameters such as HOMA-IR, both in patients with or without hyperuricemia, these drugs could be new class potential in treating patients with metabolic syndrome. Objectives: evaluate allopurinol effect on oxidative stress and insulin resistance in individuals with Metabolic Syndrome. Justification: the hypothesis is that metabolic syndrome individuals, due to their state of oxidative stress will benefit from treatment. As a result, their insulin response will be improved, leading to a lower risk for cardiovascular disease and diabetes. The hypothesis is based on previous studies that demonstrate the allopurinol inhibition of XO system and ADPH, related to oxidative stress, reducing ROS. It Supports the hypothesis that allopurinol may be incurred in drugs indicated for the treatment of MS. This study is a prospective clinical trial and will include patients treated in outpatient League of Metabolic Syndrome (Department of Endocrinology, Hospital of Clinics, School of Medicine-University of São Paulo ), which will be invited to participate in the project. Those who show interest in participating will sign a Statement of Informed Consent, after a detailed explanation of the purpose of the study, and the indications and consequences of treatment with allopurinol. Patients will be informed about the lack of mandatory participation and the availability of the institution to continue with their treatment, regardless of their participation.60 patients with the metabolic syndrome of both genders will be selected, aged 30-60 years. They will be divided into two groups according to serum uric acid concentrations. Group 1: 30 patients with metabolic syndrome and normal uric acid (up to 5.00 mg/dl), Group 2: 30 patients with metabolic syndrome and hyperuricemia (d12.00 and 7.00) mg/dl. The diagnosis of MS is defined according to the classification of the International Diabetes Federation (IDF) (20) and hyperuricemia (according to criteria of the American College of Rheumatology). We will study the patients enrolled in the League of Metabolic Syndrome in the Department of Endocrinology, Hospital of Clinics, School of Medicine-University of São Paulo (HCFMUSP). The study will include the analysis in the Research Ethics Committee, HCFMUSP1.A - Inclusion criteria -A - Provide at least three of the following characteristics Both sexesAge 30-60Waist(cm): 92 (men) and 88 (women)High-density lipoprotein (HDL)(mg / dl): >40 (man) ; >50 (women)TG (mg / dl) : >150Fasting glucose (mg / dl): >110 impaired glucose tolerance on 2 hour OGTT (mg/dl): <126 and >140Systolic blood pressure(mmHg): >135Diastolic blood pressure(mmHg): >85Both sexes Age 30-60. (AU)