Effetto di tireomimetici selettivi e di tironamine sul metabolismo energetico e sul danno ossidativo di tessuti di ratto.

Effect of T1AM and selective thyromimetics on energy metabolism and oxidative injury. In vertebrates thyroid hormone stimulates oxygen consumption, and hyperthyroidism is associated with oxidative injury in T3 target tissues, such as liver, heart and skeletal muscle. We plan to use TR-beta agonists (GC-1 e GC-24), TR-alpha antagonists (HY-4), and TR-beta antagonists (NH3) to discriminate the role of TR-alpha and TR-beta with regard to oxygen consumption. Similar experiments will be performed with T1AM, and the influence of T1AM on glucose and palmitate uptake will be determined in adipocytes, both in the absence and in the presence of insulin and/or T3. As a complement to the metabolic investigations we will evaluate the effect of T1AM on feeding and water consumption after intraperitoneal injection and after direct hypothalamic injection in normal and diabetic mice. We also plan to acertain the effect of selective thyromimetics and T1AM on mitochondrial function and on the determinants of oxidative injury - i.e. reactive oxygen species (ROS) production, scavenging enzymes and low molecular weight antioxidants - determined in cardiac, liver and skeletal muscle mitochondria.