Effects of Thyroid State on H₂O₂ Production by Rat Heart Mitochondria: Sites of Production with Complex I- and Complex II-Linked Substrates

Abstract

This work was designed to determine possible effects of altered thyroid states on rates and sites of H₂O₂ production by rat heart mitochondria. Rates of O₂ consumption and H₂O₂ release, capacities to remove the peroxide, lipid peroxidation, cytochrome oxidase activities and ubiquinone levels were determined in heart mitochondria from euthyroid, hypothyroid, and hyperthyroid rats. Hypothyroidism decreased, whereas hyperthyroidism increased the rates of O₂ consumption and H₂O₂ release during both state 4 and state 3 respiration with Complex I- or Complex II-linked substrates. The percentage of O₂ released as H₂O₂ was not significantly affected by thyroid state. However, the mitochondrial capacity to remove H₂O₂ increased in the transition from hypothyroid to hyperthyroid state, which indicates that H₂O₂ production did not modify in proportion to the rate of O₂ consumption. The thyroid-state-linked changes in H₂O₂ production were well correlated with the levels of hydroperoxides. Rates of H₂O₂ release in the presence of respiratory inhibitors indicated that changes in the H₂O₂ production occurred at both sites at which H₂O₂ was generated in euthyroid state. This result and the observation that ubiquinol levels and cytochrome oxidase activities increase in the transition from hypothyroid to hyperthyroid state suggest that the modifications of H₂O₂ production are due to a modulation by thyroid hormone of mitochondrial content of autoxidisable electron carriers.

Thyroid Hormone - Oxidative Stress - Free Radicals - H₂O₂ Release - Heart Mitochondria - Coenzyme Q

References

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