Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA inthe mouse heart

Oxygen radicals of mitochondrial origin are involved in oxidative damage. I n order to analyze the possible relationship between metabolic rate, oxidat ive stress and oxidative damage, OF1 female mice were rendered hyper- and h ypothyroid by chronic administration of 0.0012% L-thyroxine (T-4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid pe roxidation in the heart, although the endogenous levels of lipid peroxidati on were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochond rial DNA was greater than that to genomic DNA. Hyperthyroidism. decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly dec reased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to l ipids and DNA, and cellular redox potential in the mouse heart. A higher ox idative stress in the hyperthyroid group is presumably neutralized in the c ase of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxid ative damage in the different cell compartments.