Effect of thyroid state on H2O2 production by rat liver mitochondria.
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 O2 consumption and H2O2 release by rat liver mitochondria were investigated. Hypothyroidism decreased the rates of O2 consumption and H2O2 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 O2 released as H2O2 was not significantly affected by thyroid state. On the other hand, the capacity of mitochondria to remove H2O2 increased by about 17% in hyperthyroid rats and decreased by about 35% in hypothyroid ones. This result indicates that the ratio between H2O2 production and release and so the percentage of O2 turned into H2O2 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 H2O2 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 H2O2 release in the presence of respiratory inhibitors, which show that the thyroid state-linked changes in H2O2 production occur at H2O2 generator sites of both Complex I and Complex III.
Venditti
Paola
P
Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli, I-80134 Napoli, Italy.
De Rosa
Raffaella
R
Di Meo
Sergio
S
D000818:Animals; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*
D012402:Rotenone; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV