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Thyronamines T0AM and T1AM are naturally occurring decarboxylated thyroid hormone derivatives. Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature. Since the mitochondrial energy-transduction apparatus is known to be a potential target of thyroid hormone and its derivatives, we investigated the in vitro effects of T0AM and T1AM on the rates of O2 consumption and H2O2 release by rat liver mitochondria. Hypothyroid animals were used because of the low levels of endogenous thyronamines. We found that both compounds are able to reduce mitochondrial O2 consumption and increase H2O2 release. The observed changes could be explained by a partial block, operated by thyronamines, at a site located near the site of action of antimycin A. This hypothesis was confirmed by the observation that thyronamines reduced the activity of Complex III where the site of antimycin action is located. Because thyronamines exerted their effects at concentrations comparable to those found in hepatic tissue, it is conceivable that they can affect in vivo mitochondrial O2 consumption and H2O2 production acting as modulators of thyroid hormone action.

SUMMARYExposure of homeothermic animals to low environmental temperature is associated with oxidative stress in several body tissues. Because cold exposure induces a condition of functional hyperthyroidism, the observation that tissue oxidative stress also happens in experimental hyperthyroidism, induced by 3,5,3Ј-triiodothyronine (T 3 ) treatment, suggests that this hormone is responsible for the oxidative damage found in tissues from cold-exposed animals. Examination of T 3 -responsive tissues, such as brown adipose tissue (BAT) and liver, shows that changes in factors favoring oxidative modifications are similar in experimental and functional hyperthyroidism. However, differences are also apparent, likely due to the action of physiological regulators, such as noradrenaline and thyroxine, whose levels are different in cold-exposed and T 3 -treated animals. To date, there is evidence that biochemical changes underlying the thermogenic response to cold as well as those leading to oxidative stress require a synergism between T 3 -and noradrenaline-generated signals. Conversely, available results suggest that thyroxine (T 4 ) supplies a direct contribution to cold-induced BAT oxidative damage, but contributes to the liver response only as a T 3 precursor.

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