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Effetto di tireomimetici selettivi e di tironamine sul metabolismo energetico e sul danno ossidativo di tessuti di ratto.
No full textEffect 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
Thyroid hormone-induced oxidative stress
No full textHypermetabolic state in hyperthyroidism is associated with tissue oxidative injury. Available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS production. The increased mitochondrial ROS generation is a side effect of the enhanced level of electron carriers, by which hyperthyroid tissues increase their metabolic capacity. Investigations of antioxidant defence system have returned controversial results. Moreover, other thyroid hormone-linked biochemical changes increase tissue susceptibility to oxidative challenge, which exacerbates the injury and dysfunction they suffer under stressful conditions. Mitochondria, as a primary target for oxidative stress, might account for hyperthyroidism linked tissue dysfunction. This is consistent with the inverse relationship found between functional recovery of ischemic hyperthyroid hearts and mitochondrial oxidative damage and respiration impairment. However, thyroid hormone-activated mitochondrial mechanisms provide protection against excessive tissue dysfunction, including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulate opening of permeability transition pores
Evolution of the Knowledge of Free Radicals and Other Oxidants
Full text linkFree radicals are chemical species (atoms, molecules, or ions) containing one or more unpaired electrons in their external orbitals and generally display a remarkable reactivity. The evidence of their existence was obtained only at the beginning of the 20th century. Chemists gradually ascertained the involvement of free radicals in organic reactions and, in the middle of the 20th century, their production in biological systems. For several decades, free radicals were thought to cause exclusively damaging effects . This idea was mainly supported by the finding that oxygen free radicals readily react with all biological macromolecules inducing their oxidative modification and loss of function. Moreover, evidence was obtained that when, in the living organism, free radicals are not neutralized by systems of biochemical defences, many pathological conditions develop. However, after some time, it became clear that the living systems not only had adapted to the coexistence with free radicals but also developed methods to turn these toxic substances to their advantage by using them in critical physiological processes. Therefore, free radicals play a dual role in living systems: they are toxic by-products of aerobic metabolism, causing oxidative damage and tissue dysfunction, and serve as molecular signals activating beneficial stress responses. This discovery also changed the way we consider antioxidants. Their use is usually regarded as helpful to counteract the damaging effects of free radicals but sometimes is harmful as it can block adaptive responses induced by low levels of radicals
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