EFFECT OF THYROID STATE ON CHARACTERISTICS DETERMINING THE SUSCEPTIBILITY TO OXIDATIVE STRESS OF MITOCHONDRIAL FRACTIONS FROM RAT-LIVER

We have studied biochemical and functional characteristics of three mi tochondrial fractions resolved by differential centrifugation from the liver of rats in different thyroid states. In particular, the relatio n between cytochrome and antioxidant content of the mitochondria and t heir oxygen consumption and response to oxidative stress has been inve stigated. The cytochrome content is greater in the fractions at higher density, whereas the opposite pattern is shown for antioxidant level. These biochemical characteristics seem to determine functional ones. In fact, the fraction at higher density exhibit greater oxygen consump tion and smaller capacity for opposing a oxidative stress. A similar d ependence of functional characteristics on biochemical ones was found in altered thyroid states. Hypothyroidism is associated with decreased cytochrome content and oxygen consumption and increased antioxidant l evel and effectiveness in responding to oxidative stress. The treatmen t of thyroidectomized rats with triiodothyronine leads to reversion of such a pattern. We are inclined to explain the differences in suscept ibility to oxidative stress of the mitochondria by a modulation exerte d by thyroid hormone, during the normal maturation process, on their c ytochrome content. In effect, such a content is able to determine both respiratory characteristics and sensitivity to pro-oxidants of mitoch ondria. This sensitivity and the decrease of antioxidants, possibly du e to free radical production associated with the increased oxygen flux , make the mitochondria less able to respond to an oxidative challenge .