The Link Between Oxidative Stress Response and Tumor Necrosis Factor-Alpha (TNF-alpha) in Hepatic Tissue of Rats With Induced Thyroid Dysfunction

Abstract

Thyroid hormones are essential for normal organ growth, development and function. They regulate the basal metabolic rate of different types of cells, including hepatocytes. Oxidative stress plays an essential role in the pathogenesis of thyroid disorders and disturbed tissue functions. Tumor necrosis factor-alpha (TNF-α) is a cytokine with numerous immunological and metabolic activities. Several studies relate this cytokine to thyroid dysfunction and chronic liver diseases. This study aims to determine the relationship between the oxidative stress and the hepatic inflammatory cytokines TNF-α in rats with disturbed thyroid functions. Also, to investigate how this can affect normal hepatic tissues. Twenty-seven rats were divided into three groups: euthyroid group, hyperthyroid group; hyperthyroidism was induced by daily intraperitoneal injection of L-thyroxine and hypothyroid group; hypothyroidism was induced by administering propylthiouracil using oral gastric tube. At the end of the experiments, rats were fasted for 12 hours then blood samples were collected to measure the level of free T₃, free T₄, TSH, serum malondialdehyde (MDA), and total antioxidant (TAC). Then animals were scarified by cervical decapitation, slices of livers were submitted to histopathological examination, the rest of liver tissues were extracted and homogenized for measurements of TNF-α. The data showed that serum MDA was significantly elevated while TAC levels were significantly decreased in both hyperthyroid and hypothyroid groups compared to their corresponding values in euthyroid group. TNF-α level was also significantly increased in hyperthyroid and hypothyroid groups compared to its level in euthyroid group. Histopathological examination of the liver revealed prominent lymphocytic infiltration with some aggregate formation in portal tract in both hypothyroid and hyperthyroid groups. The lymphocytic infiltrate was more prominent in hypothyroid rats compared to the hyperthyroid rats. This study suggests that the oxidative stress and elevated level of TNF-α play an essential role in hepatic cell injury associated with thyroid dysfunction. A complex relationship exists between the thyroid gland and the liver in health and disease.

Keywords: Thyroid dysfunction, oxidative stress, hepatic tissue, rats TNF-α