Thyroid state affects H2O2 removal by rat heart mitochondria (original) (raw)
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Molecular and cellular endocrinology, 2015
We investigated thyroid state effect on capacity of rat liver mitochondria to remove exogenously produced H2O2, determining their ability to decrease fluorescence generated by an H2O2 detector system. The rate of H2O2 removal by both non respiring and respiring mitochondria was increased by hyperthyroidism and decreased by hypothyroidism. However, the rate was higher in the presence of respiratory substrates, in particular pyruvate/malate, indicating a respiration-dependent process. Generally, the changes in H2O2 removal rates mirrored those in H2O2 release rates excluding the possibility that endogenous and exogenous H2O2 competed for the removing system. Pharmacological inhibition revealed thyroid state-linked differences in antioxidant enzyme contribution to H2O2 removal which were consistent with those in antioxidant system activities. The H2O2 removal was only in part due to enzymatic systems and that imputable to non-enzymatic processes was higher in hyperthyroid and lower in ...
Effect of thyroid state on H2O2 production by rat liver mitochondria
Molecular and cellular endocrinology, 2003
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 r...
Effect of thyroid state on rate and sites of H2O2 production in rat skeletal muscle mitochondria
Archives of Biochemistry and Biophysics, 2003
The purpose of this study was to investigate the effects of thyroid state on rates and sites of H 2 O 2 production in rat muscle mitochondria. With Complex I-and Complex II-linked substrates, hypothyroidism decreased and hyperthyroidism increased the rates of O 2 consumption during State 4 and State 3 respiration and the rates of H 2 O 2 release during State 4 respiration. During State 3, the rates of H 2 O 2 release were not affected by thyroid state. However, the mitochondrial capacity to remove H 2 O 2 increased in the transition from hypothyroid to hyperthyroid state, thus suggesting that an increase in H 2 O 2 production rate also occurred in such a transition during State 3 respiration. The observation that mitochondrial coenzyme Q levels and cytochrome oxidase activities are higher in the hyperthyroid and lower in the hypothyroid groups suggests that the modifications of H 2 O 2 production are due to a modulation by thyroid hormone of the mitochondrial content of autoxidizable electron carriers. This idea is supported by measurements of H 2 O 2 release in the presence of respiratory inhibitors. In fact, such measurements indicate that the thyroid state-linked changes in H 2 O 2 production occur at both generator sites of the respiratory chain.
Effect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues
Free Radical Biology and Medicine, 2003
The effects of the thyroid state on oxidative damage, antioxidant capacity, susceptibility to in vitro oxidative stress and Ca 2ϩ -induced permeabilization of mitochondria from rat tissues (liver, heart, and gastrocnemious muscle) were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 d. Hyperthyroidism was elicited by a 10 d treatment of hypothyroid rats with triiodothyronine (10 g/100 g body weight). Mitochondrial levels of hydroperoxides and protein-bound carbonyls significantly decreased in hypothyroid tissues and were reported above euthroid values in hypothyroid rats after T 3 treatment. Mitochondrial vitamin E levels were not affected by changes of animal thyroid state. Mitochondrial Coenzyme Q9 levels decreased in liver and heart from hypothyroid rats and increased in all hyperthyroid tissues, while Coenzyme Q10 levels decreased in hypothyroid liver and increased in all hyperthyroid tissues. The antioxidant capacity of mitochondria was not significantly different in hypothyroid and euthyroid tissues, whereas it decreased in the hyperthyroid ones. Susceptibility to in vitro oxidative challenge decreased in mitochondria from hypothyroid tissues and increased in mitochondria from hyperthyroid tissues, while susceptibility to Ca 2ϩ -induced swelling decreased only in hypothyroid liver mitochondria and increased in mitochondria from all hyperthyroid tissues. The tissue-dependence of the mitochondrial susceptibility to stressful conditions in altered thyroid states can be explained by different thyroid hormone-induced changes in mitochondrial ROS production and relative amounts of mitochondrial hemoproteins and antioxidants. We suggest that susceptibilities to oxidants and Ca 2ϩ -induced swelling may have important implications for the thyroid hormone regulation of the turnover of proteins and whole mitochondria, respectively.
Molecular and Cellular Endocrinology, 2006
Hyperthyroidism was induced in rats by l-thyroxine administration (12 mg/L in drinking water, 4 weeks). Animals were assessed hemodynamically, and heart, lung, and liver morphometry were performed. Lipid peroxidation (LPO) and protein oxidation (carbonyls) were measured in heart homogenates. It was quantified glutathione (GSH) metabolism, and antioxidant enzyme activities its and protein expression (by Western blot). At the end of treatment, it was observed cardiac hypertrophy, elevation of left ventricular systolic and end diastolic pressures, lung and liver congestion. LPO and carbonyls were increased in the hyperthyroid group, and GSH was decreased by 46% in the fourth week. Myocardial oxidative stress time course analysis revealed that it was increased in the second week of treatment. Antioxidant enzyme activities elevation was accompanied by protein expression induction in the hyperthyroid group in the fourth week. These results imply that hyperthyroidism generates myocardial dysfunction associated with oxidative stress inducing antioxidant enzyme activities and protein expression.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1994
In order to further investigate the mechanism regulating the control of mitochondrial respiration by thyroid hormones, the effect of the hyperthyroidism on the kinetic characteristics of cytocrome c oxidase in rat heart mitochondria was studied. Mitochondrial preparations from both control and hyperthyroid rats had equivalent g m values for cytochrome c, while the maximal activity of cytochrome oxidase was significantly increased (by around 30%) in mitochondrial preparation from hyperthyroid rats. This enhanced activity of cytochrome oxidase was associated to a parallel increase in mitochondrial State 3 respiration. The hormone treatment resulted in a decrease in the flux control coefficent of the oxidase. The enhanced activity of cytochrome oxidase in hyperthyroid rats does not appear to be dependent on an increase in the mass of this enzyme complex in that the heme aa 3 content was equivalent in both hyperthyroid and control preparations. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hyperthyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a lower temperature. Cardiolipin content was significantly increased in mitochondrial preparations from hyperthyroid rats, while there were no significant alterations in the fatty acid composition of cardiolipin of control and hyperthyroid preparations. The results support the conclusion that the enhanced cytochrome oxidase activity in heart mitochondrial preparations from hyperthyroid rats is due to a specific increase in the content of cardiolipin.
Molecular and Cellular Endocrinology, 2000
Mitochondria seem to be involved in oxygen radical damage and aging. However, the possible relationships between oxygen consumption and oxygen radical production by functional mitochondria, and oxidative DNA damage, have not been studied previously. In order to analyze these relationships, male Wistar rats of 12 weeks of age were rendered hyper-and hypothyroid by chronic T 3 and 6-n-propyl-2-thiouracil treatments, respectively. Hypothyroidism decreased heart mitochondrial H 2 O 2 production in States 4 (to 51% of controls; P B0.05) and 3 (to 21% of controls; PB 0.05). In agreement with this, 8-oxo-7,8-dihydro-2%-deoxyguanosine (8-oxodG) decreased in the heart genomic DNA of hypothyroid animals to 40% of controls (PB0.001). Studies with respiratory inhibitors showed that the decrease in oxygen radical generation observed in hypothyroidism occurred at Complex III (mainly) and at Complex I; that decrease was due to the presence of a lower free radical leak in the respiratory chain (P B 0.05). Hyperthyroidism did not significantly change heart mitochondrial H 2 O 2 production since the increase in State 4 oxygen consumption in comparison with control and hypothyroid animals (PB 0.05) was compensated by a decrease in the free radical leak in relation to control animals (PB 0.05). In agreement with this, heart 8-oxodG was not changed in hyperthyroid animals. The lack of increase in H 2 O 2 production per unit of mitochondrial protein will protect mitochondria themselves against self-inflicted damage during hyperthyroidism.
The impact of thyroid activity variations on some oxidizing-stress parameters in rats
Comptes Rendus Biologies, 2007
The effect of the thyroid activity on the formation of lipid peroxidation and on liver and heart antioxidant enzyme activities was investigated in Wistar rats. Hypothyroidism and hyperthyroidism conditions were induced for five weeks by the administration of 0.05% benzythiouracile (BTU) and L-thyroxine sodium salt (0.0012%), in drinking water, respectively. No significant effect was observed on the rates of both lipid peroxidation and the vitamin E in hepatic and cardiac tissues of hypothyroidism rats compared to the controls, contrary to the hyperthyroidism rats, which expressed a pronounced increase. The increased glutathione peroxydase activity in rats suffering from hyperthyroidism was associated with a fall of the reduced glutathione in the homogenate and a marked increase in the glutathione reductase activity. An increase in superoxyde dismutase and catalase activities was also recorded in hyperthyroidism. Our results explain the thyroid activity variation in relation to the lipid peroxidation and the tissular contents of the enzymatic and the non-enzymatic antioxidants. To conclude, our results show the occurrence of a state of oxidizing stress in relation to hyperthyroidism. To cite this article: M.
Thyroid Hormones in Excess Induce Oxidativestress in Rats
Acta Endocrinologica (Bucharest), 2009
Thyroid hormones play a crucial role in the regulation of the mitochondrial oxidative metabolism. Hyperthyroidism caused by the acceleration of the energy metabolism leads to the occurrence of cellular oxidative stress. The aim is to evaluate the pro-oxidant / antioxidant balance and the effect of vitamin E supplementation in damage caused by the excessive administration of thyroid hormones. Materials and Methods. White, male Wistar rats were used in the study. Thirty male Wistar rats were divided into three groups (1:control group, 2:animals treated with L-Thyroxine 10 µg/animal/day for 30 days, 3:L-Thyroxin treated rats protected with vitamin E 10 mg/animal/day). Malondialdehyde (MDA), the marker of lipid peroxidation, carbonyl proteins, SH groups, glutathione (GSH) and superoxide dismutase (SOD) were determined from the serum, while MDA, carbonyl proteins, SH groups and GSH were determined from the thyroid tissue homogenates. The results showed increased levels of carbonyl proteins (1.31±0.33 nmol/mg protein, p=0.0001) in serum in thyrotoxic group versus control, while MDA levels did not differ significantly from the control. Significantly low values of the SH groups, GSH and SOD were found (p<0.001) in the plasma of Thyroxin treated rats. Vitamin E supplementation significantly increased plasma MDA levels in the Thyroxin treated group as compared with the control group (p=0.01) and with the animals treated only with Thyroxin (p=0.04). Carbonyl protein levels in plasma of the hyperthyroid supplemented rats were also increased as compared to controls (p=0.0002). Antioxidant capacity markers in plasma of group 3 were decreased compared with group 1. The marker of lipid peroxidation (MDA) significantly decreased in thyroid homogenates of the group 2 as compared with group 1 (p=0.004). Significantly high levels of the SH groups (p=0.0006) and low levels of GSH (p=0.0001) were found in thyroid homogenates of the L-Thyroxin treated group as compared with controls. These results suggest that experimental hyperthyroidism is accompanied with increased oxidative stress and with the consumption of antioxidant enzymes in induced oxidative aggressions. No protective effects of vitamin E on oxidative stress induced by excessive administration of thyroid hormones were detected.