Reduced brain glucose with normal plasma glucose in salicylate poisoning

Abstract

A BS T R A C T After the intraperitoneal injection into young mice of 700-800 mg/kg of salicylate, brain glucose fell to one-third or less of control values despite normal plasma glucose levels; brain lactate was nearly doubled and there were small decreases in phosphocreatine (18%) and in glycogen (17%). ATP, pyruvate, a-ketoglutarate, and glutamate were unchanged. In liver, glycogen was reduced 79% and lactate was five times higher than in control animals; glucose, glucose-6-phosphate, and ATP were unchanged.Since salicylate uncouples oxidative phosphorylation, it is postulated that high energy phosphate in the brain is maintained near normal levels by a compensatory increase in cerebral glycolysis. Apparently the brain glucose level falls because the rate of utilization exceeds the rate at which glucose can be supplied from the blood. Concurrent administration of glucose with salicylate elevated brain glucose concentration and was associated with striking improvement in the condition and the increased survival of the animals. These findings stress the fact that in salicylate poisoning the supply of glucose to the brain may be inadequate even when blood glucose levels are normal.

Effect of nonsteroidal anti‐inflammatory drugs on glycogenolysis in isolated hepatocytes

“…However, direct comparison of the in vitro concentrations used and those seen in vivo is difficult because the drugs are highly protein bound (Metz, 1981) and the more important free drug concentration is not known. Salicylate intoxication is well known to be associated with enhanced hepatic glycogenolysis (Thurston et al, 1970). Several mechanisms have been suggested to explain salicylateinduced glycogenolysis (Thurston et al, 1970), but it is interesting to note that salicylate is a carboxylic acid and would be expected to have effects similar to those described here for ibuprofen, meclofenamate and indomethacin.…”

“…Salicylate intoxication is well known to be associated with enhanced hepatic glycogenolysis (Thurston et al, 1970). Several mechanisms have been suggested to explain salicylateinduced glycogenolysis (Thurston et al, 1970), but it is interesting to note that salicylate is a carboxylic acid and would be expected to have effects similar to those described here for ibuprofen, meclofenamate and indomethacin.…”

Acid-Base Balance

“…Glucose infusions are used to increase the cerebrospinal fluid concentration of glucose, which is frequently decreased. 52 Volatile alcohol ingestions are frequent causes of metabolic acidosis, most commonly methanol, isopropanol, or ethylene glycol. Methanol (rubbing alcohol) is converted to formic acid, and ethylene glycol (radiator fluid) is converted to oxalic acid and other toxic anions.…”

Toxicology Today

“…97 Salicylate neurotoxicity has also been correlated with decreased CNS glucose concentrations despite normal serum glucose concentrations. 95,98 Therefore, dextrose should be considered in any patient presenting with altered mental status and suspected salicylate toxicity. Uncoupling of oxidative phosphorylation may further result in increased heat production and the inability to dissipate heat.…”