PREVENTION BY ASCORBIC ACID OF LIVER GLYCOGEN DEPLETION IN ENDOTOXIN INTOXICATION.

Abstract

IT is well established that there is a striking depletion of liver glycogen in endotoxin intoxication, and insulin, glucose and lactate are relatively ineffective in increasing liver glycogen storage1. This depletion of liver glycogen is not necessarily due to epinephrine discharge or to circulatory disturbances attendant on intoxication, but it seems to be related to the accumulation of endotoxin in liver2. The characteristic prostration common to all animal species in the later stage of endotoxin intoxication seems to be related to this depletion of glycogen2. It is especially pronounced in adrenalectomized animals, and death results from hypoglycaemic deterioration with or without cramp. It is well known that pretreatment with cortisone prevents death1. Although the mechanism of glycogen depletion has been discussed in relation to inhibition of hepatic enzymes, especially succinic dehydrogenase3, or to the effect on mitochondria leading to oxidative uncoupling4, no conclusive evidence indicating special relations of endotoxin to these disturbances could be obtained. In this respect it has been shown that the effect of endotoxin in depleting liver glycogen in rabbits is much lessened in the hot summer season even in adrenalectomized animals5. It has therefore been suggested that the depletion of liver glycogen might be determined by the metabolic response of liver induced by the uptake of endotoxin in the hepatic reticuloendothelial cells. Here it was shown that saturation with ascorbic acid could ameliorate the depletion of liver glycogen in cold weather in which the susceptibility of the animal is markedly enhanced.