The effect of thyroid hormone treatment on hepatic microsomal functions related to NADPH-dependent electron transfer reactions was studied in rats given 0.1 mg T3/kg BW for 1, 2, 3, and 7 consecutive days. This treatment resulted in increased rates of O2-. generation by microsomal fractions, concomitantly with an enhancement in NADPH oxidase activity and decreased cytochrome P-450 content, in livers exhibiting increased respiration. Subsequent studies showed elevated levels of malondialdehyde in microsomal fractions and liver homogenates, as well as augmented chemiluminescent response in the latter system. These results indicate that the calorigenic effect of T3 on the liver tissue is accompanied by a stimulation of microsomal functions involving univalent reduction of oxygen. This cellular response might lead to a greater lipid peroxidative rate and cytochrome P-450 loss as secondary events of thyroid hormone action.

Chemiluminescent and respiratory responses were studied in the liver of rats treated with 0.1 mg of triiodothyronine (T3)/kg for 1 to 7 days. Hyperthyroidism resulted in significant increments in the spontaneous chemiluminescence of the in situ liver in animals exhibiting a calorigenic response. Microsomal NADPH-dependent oxygen uptake was enhanced by T3 treatment for 2 days, an effect that was completely abolished by the antioxidant cyanidanol. A similar microsomal antioxidant-sensitive respiratory component was observed in this situation after the addition of t-butyl hydroperoxide (t-BHP). However, basal rates of microsomal oxygen uptake and light emission in liver homogenates and microsomes were decreased by t-BHP, probably related to thyroid hormone-induced diminution in the content of cytochrome P-450 (Fernández et al.) In addition, liver superoxide dismutase and catalase activities as well as the total content of glutathione were depressed by T3. These results indicate that the calorigenic response in the hyperthyroid state is accompanied by the development of an hepatic oxidative stress characterized by enhanced spontaneous chemiluminescence, enhanced NADPH-dependent microsomal respiration and a decreased antioxidant cellular activity.