Toxicity of a fatty acid and ammonia: interactions with hypoglycemia and Krebs cycle inhibition.

In rats, hypoglycemia induced with insulin and Krebs cycle inhibition produced by fluoroacetate poisoning augmented the encephalopathic effects of octanoic acid and NH4Cl. Blood sugars in the range of 25 to 45 mg/dl resulted in a decrease of approximately 30% in the doses of NH+4 and of octanoate required to induce coma in otherwise normal rats. Mild fluoroacetate poisoning resulted in a corresponding decrease of 25% in the dose of NH+4 and 10% in the dose of octanoate. A single coma-inducing dose of octanoate or several subcoma doses resulted in blood sugar decrements of 50% or more within 1 to 3 hr. A combination of subcoma doses of octanoate and NH+4 had the same effect. Pretreatment with glucose prevented the hypoglycemia and blunted the encephalopathic response to octanoate. A single coma-inducing dose of NH+4 or several subcoma doses resulted in blood sugar increments of 50% or more within 1/2 to 5 hr.