Effect of thyroid state on H 2O 2 production by rat liver mitochondria

Abstract

It has been suggested that activation of mitochondrial respiration by thyroid hormone results in oxidative tissue injury secondary to increased reactive oxygen species production. In order to throw light on this subject, the effects of thyroid state on O 2 consumption and H 2O 2 release by rat liver mitochondria were investigated. Hypothyroidism decreased the rates of O 2 consumption and H 2O 2 release by succinate or pyruvate/malate-supplemented mitochondria during both State 4 and State 3 respiration, whereas hyperthyroidism increased such rates. Conversely, with both substrates and during either respiration phase, the percentage of O 2 released as H 2O 2 was not significantly affected by thyroid state. On the other hand, the capacity of mitochondria to remove H 2O 2 increased by about 17% in hyperthyroid rats and decreased by about 35% in hypothyroid ones. This result indicates that the ratio between H 2O 2 production and release and so the percentage of O 2 turned into H 2O 2 instead of being reduced to water increase in the transition from hypothyroid to hyperthyroid state. In light of previous observations that mitochondrial content of cytochromes and ubiquinone also increases in such a transition, the modifications of H 2O 2 production appear to be due to a modulation by thyroid hormone of the mitochondrial content of the autoxidisable electron carriers. This view is supported by measurements of H 2O 2 release in the presence of respiratory inhibitors, which show that the thyroid state-linked changes in H 2O 2 production occur at H 2O 2 generator sites of both Complex I and Complex III.