The toxic action of phenothiazine and some disturbances of intermediary metabolism in undernourished sheep

Abstract

Uncoupling of oxidative phosphorylation was found in preparations of liver mitochondria obtained from adequately fed sheep, killed 24 hr after the administration of phenothiazine. Sheep fed a low quality diet suffered considerable loss of weight and all had fatty livers at necropsy. The extent of the fatty change seemed to be related to the rate of weight loss. Liver mitochondria from sheep which had lost body weight at an average of 0.3 lb/day had normal biochemical activities. The administration of phenothiazine to such sheep caused uncoupling of oxidative phosphorylation. Animals with weight losses of 0.33 lb day or more showed depressed mitochondria] respiration rates with very little phosphorylation. Phenothiazine did not increase the Q(N)O2 values in such sheep. Glucose 6-phosphate dehydrogenase activity was found to be extremely low in sheep erythrocytes—approximately 5% of normal human red cell values. The activity of this enzyme was not affected by malnutrition, or by phenothiazine administration to either well-fed or undernourished sheep.