This study was designed to determine if peroxidation of biomembrane lipid and the protective system can be modified by the change in oxidative metabolism induced by thyroid dysfunction. The free radical scavengers (i.e. cuprozinc cytosolic and mangano mitochondrial superoxide dismutases, glutathione peroxidase, and catalase), mitochondrial oxidative marker enzymes (cytochrome c oxidase and fumarase), and lipid peroxide were measured in liver, heart, soleus (slow oxidative), and extensor digitorum longus (fast glycolytic) muscles. Rats were rendered hyper- or hypothyroid for 4 weeks and then killed. Superoxide dismutases were detected by specific RIAs: catalase by polarography, and lipid peroxide by fluorimetry. Hypothyroid rats failed to grow, while hyperthyroid rats had hypertrophied hearts but no growth failure. An increase in lipid peroxide was observed in the soleus and heart muscles of hyperthyroid rats. This was accompanied by an increase in mitochondrial superoxide dismutase and oxidative markers. No such change was observed in either fast glycolytic muscle or liver. Glutathione peroxidase decreased in all tissues of hyperthyroid rats, and there was a parallel decrease in catalase in most tissues. On the other hand, hypothyroidism induced a reduction in oxidative markers and mitochondrial superoxide dismutase in heart and skeletal muscles, but only a marginal change in lipid peroxidation. The cytosolic superoxide dismutase did not change in relation to either oxidative metabolism or lipid peroxidation. These results suggest that the enhanced oxidative metabolism and decreased glutathione peroxidase in hyperthyroidism result in an increase in lipid peroxidation and, in slow oxidative and heart muscle, possible organ damage. No adverse reaction mediated by active oxygen species was found in hypothyroid rat tissues.

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SummaryTo determine whether vitamin E protects against thyroxine induced oxidative stress in heart and soleus (slow oxidative) muscles, lipid peroxide (thiobarbituric acid-reactive substances) and antioxidant enzymes were measured in those tissues of hyperthyroid rats supplemented with vitamin E. The rats were rendered hyperthyroid by the administration of L-thyroxine in their drinking water. In experiment (EXPT) I, 30mg/kg/dose of alpha-tocopheryl acetate was administered to the vitamin E-treated group. In EXPT II, the rats were fed a diet containing either <1IU/kg (deficient diet), 20IU/kg (control E diet), or 500IU/kg (high E diet) of vitamin E and hyperthyroidism was induced. In EXPT I, hyperthyroidism induced an increase in oxidative enzymes, mitochondrial superoxide dismutase and lipid peroxide level, and a decrease in cytosolic superoxide dismutase, glutathione peroxidase and catalase in both tissues. Vitamin E treatment inhibited the increase in lipid peroxide level totally in the heart and partially in the soleus, with minimal changes in the other biochemical indices studied. In EXPT II, the lipid peroxide level was markedly increased in both tissues of the vitamin E-deficient group, and decreased in those of the group fed high E diet. There were some adaptive changes in the levels of cytosolic superoxide dismutase, glutathione peroxidase, and catalase in response to vitamin E deficiency, whereas neither oxidative enzymes nor mitochondrial superoxide dismutase were altered. These results suggest that vitamin E protects against lipid peroxidation in hyperthyroid heart and skeletal muscle independently of the changes in oxidative enzymes and antioxidant enzymes.

ABSTRACT. The immaturity of antioxidant capacity in sion injury involving a variety of organs including heart (2) and the lung in preterm newborn infants is postulated to con-kidney (3). The antioxidant enzymes, comprised of cytosolic tribute to the development of hyperoxic lung injury. An-CuZnSOD, mitochondrial MnSOD (EC 1.15.1. I), GPX (EC tioxidant enzymes in fetal lung, comprised of copper-zinc 1.1 1.1.9), and CAT (EC 1.1 1.1.6), afford protection by reducing (cytosolic) and manganese (mitochondrial) superoxide dis-the cellular concentration of active oxygen species (4). In special mutases, glutathione peroxidase, and catalase, have been relevance to bronchopulmonary dysplasia, several previous studreported to increase during the late gestational period. To ies focused on prenatal development of pulmonary antioxidant determine whether such maturation of antioxidant capacity enzymes in the rat (5-8). The activities of total SOD, GPX, and occurs in other tissues, we have evaluated the development CAT in lung were invariably found to be low before term and of these four enzymes from d 18 to 22 of gestation in rat the low activities are considered to account, in part, for the lung, kidney, and heart. To resolve the confusion in the vulnerability of premature newborn lung to hyperoxia. However, reported levels of lung superoxide dismutases, the two the two SOD isoenzymes were measured in only two previous isoenymes were assayed separately by specific RIA. The studies (7,8) and the data were conflicting. growth of the kidney exceeded that of the whole body Part of the confusion is due to the limited sensitivity and during this period, while the growth of the lung and heart specificity of the biologic SOD activity assays generally used. The did not. The concentrations of the four antioxidant enzymes activity assays detect all SOD-like activities, and are not specific in lung and kidney increased in a stepwise manner during to each form of intracellular SOD. Furthermore, a relatively low this period, and the magnitude of the change for each concentration of MnSOD in the tissues of rats compared with enzyme was greater in the kidney than in the lung. On the that in other species (9) makes biologic activity assays more other hand, the only significant change in the concentra-prone to interference when applied to rat tissue homogenate. tions of heart antioxidant enzymes observed was a mild The specific RIA for rat MnSOD and CuZnSOD (10) have increase in the glutathione peroxidase concentration from obviated the concerns regarding activity assays for SOD, although d 20 to 22. These results suggest that the prenatal matu-they do not measure biological activity. These assays have enration of antioxidant capacity occurs earlier in the heart abled us to measure CuZnSOD and MnSOD accurately not only and later in the kidney than in the lung, and that the in fetal lung, but also in smaller tissues in fetal rat. immaturity of antioxidant capacity could make the fetal In our present study, we evaluated the development of Curat k...