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Role of monocytes and systemic oxidative stress in hyperthyreoidism

Abstract

Thyroid mainly secrets two hormones (thyroxine - T4, and triioothyronine - T3) with identical functions, differing only in the speed and intensity of their actions. Thyroid secretion of these hormones is controlled by thyrotropin or thyroid stimulating hormone (TSH). A low hormone secretion by thyroid, resulting in lower than normal basal metabolism rate, is a condition known as hypothyroidism, while n excessive hormone secretion, which may increase basal metabolism above normal levels, is called hyperthyroidism.Thyroid hormone action on target tissues leads to enhanced cellular oxidative capacity, associated with sodium-potassium bomb activation. The increase in cellular oxidative capacity may lead to an imbalance between prooxidants and antioxidants, favoring the first, leading to a condition of potential damage, called oxidative stress.Works from the literature show an enhancement of systemic oxidative stress in hyperthyroidism, in humans and in experimental models, characterized by an increase of plasma and urine lipid peroxidation products and a decrease in plasma and erythrocyte antioxidant defenses. Additionally, there is an increase in neutrophil function in human and animal hyperthyroidism. Phagocytic cell activation leads to an enhancement of oxygen uptake and subsequent reactive species release, a phenomenon called respiratory burst, which contributes to oxidative stress. Serum levels of some interleukins (IL-6 and IL-8) also correlated positively with serum levels of T3 and T4 in human hyperthyroidism. In humans, the metabolic changes observed in hyperthyroidism disappear after a few months treatment with propylthiouracil, while hormone levels normalize. In previous works from our group, hepatic oxidative stress was observed in hyperthyroid rats, jointly with Kupffer cell hyperplasia.Since peripheral blood monocytes are resident macrophage precursors and that there is a correlation between inflammatory components and thyroid hormone levels, this work aims to study circulating monocytes function and its relation to systemic oxidative stress in hyperthyroid patients, compared to normal individuals. Sixty patients will be invited to participate from this study, ages ranging from 20 to 90 years old, selected from the ambulatory of Endocrinology of UNIFESP. They will divided into two groups: thirty hyperthyroid individuals, classified as such by their circulating levels of T3, free T4 and TSH, and thirty previously thyroidectomized patients for cancer treatment, who receive enough thyroid hormone to keep their circulating TSH either at normal or a little above normal levels. A third group of 30 healthy volunteers will serve as control group and will be sex and age paired. Each patient will have total haemogram, fasting blood glucose, serum levels of total cholesterol and fractions, triglycerides, TGO, TGP and reactive C protein. Subjects with sudden thyrotoxicosis, acute inflammatory processes, smokers, patients with a previous history of severe cardiovascular problems, liver diseases, HIV+, kidney diseases, diabetes I or II, non-controlled hypertension and alcohol or drug abuse will not be included. Participants must also report not having regular uptake of anti-inflammatory drugs, aspirin or vitamin supplements or hormone replacement (estrogens or isoflavons) for the last two months.In order to evaluate oxidative stress, we will measure plasmatic concentrations of lipid peroxidation products (TBARS) and of oxidized proteins (by ELISA), as well as plasmatic levels of alpha-tocopherol, beta-carotene, lycopene, ubiquinol-10, vitamin C and uric acid, all by HPLC. Monocyte function will be assessed by: 1) basal expression of surface molecules HLA-DR, CD11b and CD18; 2) intracellular production of IL-1 alpha, IL-6 and TNF-alpha in response to LPS stimulus; and 3) intracellular oxidation of DCFH acetate, also in response to LPS stimulus. All monocyte function assays will be performed by flow cytometry techniques. (AU)