Mitochondrial glutathione in hypermetabolic rats following burn injury and thyroid hormone administration: Evidence of a selective effect on brain glutathione by burn injury

Abstract

Cerebral cortex, heart, skeletal muscle, and liver mitochondrial glutathione (GSH) levels in severely burned rats are decreased to between approximately 50% to 70% of sham-operated, normally fed controls. In semistarved rats, weight-matched with burned rats, mitochondrial GSH levels in these tissues are decreased to between approximately 70% to 91% of those in sham-operated rats. Total GSH levels in peripheral tissues and brain are decreased to approximately 60% to 65% of control levels in rats with burn injury and food restriction, suggesting a higher mitochondrial GSH turnover in burned rats than in semistarved rats, probably because of higher “stress hormone” levels in burned rats than in semistarved rats. Cerebral cortex mitochondrial GSH levels are unaffected by variations in thyroid hormone status, but liver mitochondrial GSH levels are decreased by triiodothyronine and increased by propylthiouracil. The present results suggest that mitochondrial GSH is not only regulated by the rate of GSH synthesis in the cytosol, but seems to be under hormonal influence as well; stress hormones and triiodothyronine may decrease mitochondrial GSH by increasing mitochondrial oxygen consumption with increased reactive oxygen species formation or by increasing GSH exchange between mitochondria and the cytosol. These findings may be of importance therapeutically in increasing antioxidative defenses to limit oxidative stress injury in hypermetabolic patients.