Influence of hyper- and hypothyroidism on lipid peroxidation, unsaturationof phospholipids, glutathione system and oxidative damage to nuclear and mitochondrial DNA in mice skeletal muscle

While the biochemical literature on free radical metabolism is extensive, t here is little information on the endocrine control of tissue oxidative str ess, and in the case of thyroid hormones it is mainly limited to liver tiss ue and to short-term effects on a few selected biochemical parameters. In t his investigation, chronic hypothyroidism and hyperthyroidism were successf ully induced in mice, and various oxidative-stress-related parameters were studied in skeletal muscle. In vivo and in vitro lipid peroxidation signifi cantly increased in hyperthyroidism and did not change in the hypothyroid s tate. The fatty acid composition of the major phospholipid classes was affe cted by thyroid hormones, leading to a significant decrease in total fatty acid unsaturation both in hypothyroid and hyperthyroid muscle in phosphatid ylcholine and phosphatidylethanolamine fractions. In cardiolipin, however, the double bond content significantly increased as a function of thyroid st atus, leading to a 2.7 fold increase in the peroxidizability index from eut hyroid to hyperthyroid muscle. Cardiolipin content was also directly and si gnificantly related to thyroid state across the three groups. Glutathione s ystem was not modified by thyroid state. The oxidative damage marker 8-oxo- 7,8-dihydro-2'-deoxyguanosine did not change in mitochondrial DNA, and decr eased in genomic DNA both in hypothyroid and hyperthyroid muscle. The resul ts indicate that chronic alterations in thyroid status specially affect oxi dative damage to lipids in skeletal muscle, with a probably stronger effect on mitochondrial membranes, whereas the cytosolic redox potential and DNA are better protected possibly due to homeostatic compensatory reactions on the long-term.