Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.
Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial 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 decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.
Gredilla
R
R
Department of Animal Biology II (Animal Physiology), Faculty of Biology, Complutense University, Madrid 28040, Spain.
Barja
G
G
López-Torres
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006980:Hyperthyroidism / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008929:Mitochondria, Heart / Q000235:genetics*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D013963:Thyroid Hormones / Q000502:physiology*
D004272:DNA, Mitochondrial; D008563:Membrane Lipids; D013963:Thyroid Hormones; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003576:Electron Transport Complex IV; D003849:Deoxyguanosine; D005978:Glutathione