Effect of experimental and cold exposure induced hyperthyroidism on H2O2 production and susceptibility to oxidative stress of rat liver mitochondria

To investigate the iodothyronine role in liver responses to cold, we examined metabolic and oxidative mitochondrial changes in cold-exposed, T3-treated, and T4-treated rats, which exhibit different T4 serum levels. All treatments increased mitochondrial respiration which reached the highest and lowest values after T3 and cold treatment, respectively. The T3- and T4-induced changes agreed with the respective increases in Complex IV activities, while those elicited by cold were inconsistent with increased activities of respiratory complexes. Mitochondrial capacity to produce H2O2 was the highest in T3-treated rats, whereas it was similar in T4-treated and cold-exposed rats. The effects of respiratory inhibitors suggested that T3 and T4 mainly increase the mitochondrial content of autoxidizable electron carrier of Complex I and Complex III, respectively. The indices of oxidative modifications of proteins exhibited increases consistent with the treatment effects on H2O2 production. The increases in indices of lipid peroxidation were also dependent on changes in lipid composition. The increased protein damage in treatment groups was confirmed using immunoblotting analysis, which also showed oxidative damage in a 133 kDa fraction, which was not expressed in T3-treated rats. Antioxidant levels were not related to the extent of oxidative damage as only mitochondrial GSH levels decreased in T3-treated rats. Mitochondrial susceptibility to in vitro oxidative challenge and Ca2+-induced swelling was increased by all treatments, but was the highest in T3-treated rats. In the whole, our results indicate T3 as main responsible for the changes in the mitochondrial population associated with cold exposure. However, a significant role is also played by T4, which appears to acts mainly modulating T3 effects, but also inducing some effects different from the T3 ones.