Effect of Severe Hyperthyroidism on Concentrations of Nitric Oxide-producing Enzymes in Liver of Male Rats

Introduction: Thyroid hormones play an important role in normal function of liver and hyperthyroidism can cause liver dysfunction. Thyroid hormones affect nitric oxide (NO)-producing enzymes in liver. The aim of this study is to investigate effects of hyperthyroidism on protein levels of three isoforms of NO synthase (NOS) enzymes, including endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in the liver of male rats. Materials and Methods: Twelve male Wistar rats were divided into the hyperthyroid and the control groups. Hyperthyroidism was induced by administration of 12 mg/L of levothyroxine in the drinking water of rats for a period of 21 days. NO metabolites (i.e. nitrate+nitrite or NOx) concentrations in the serum and liver as well as iNOS, eNOS, and nNOS protein levels in the liver tissue were measured on day 21. Results: Serum levels of free thyroxine and total thyroxine were significantly higher, whereas that of the thyroid stimulating hormone (TSH) was significantly lower in rats with hyperthyroidism. Compared to controls, NOx levels were significantly higher in the serum (46%) and liver tissue (70%) of rats with hyperthyroidism. Hyperthyroidism decreased protein levels of eNOS (31%, P=0.006) and increased protein levels of iNOS (26%, P=0.020) but had no effect on nNOS in the liver. Conclusion: Hyperthyroidism changed levels of NO-producing enzymes liver, indicating that dysfunction of NO system may contribute to the pathophysiology of hyperthyroidism.