Rats were fed a standard diet or the standard diet supplemented with ammonium acetate (20% w/w) for up to 100 days. The effect of the ingestion of the highammonium diet on some aspects of nitrogen metabolism in rats was studied. Ammonia levels in blood increased =3-fold; in brain, liver and muscle the increases were 36, 34 and 50%, respectively. Urea levels in blood and urea excretion increased x2-fold. There was no increase of carbamyl phosphate synthase. Liver glutamine synthase activity increased by 68% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected. Glutamine content in brain was twice that of controls. This new animal model to study hyperammonemia offers several advantages over others: it is simpler, is bloodless, requires no animal manipulation and permits long-term studies.
Hyperammonemia is considered one of the most important factors responsible for the mediation of hepatic encephalopathy. However, in spite of much work, the mechanism of ammonia toxicity has not been completely elucidated. Studies of the consequences of hyperammonemia have used portacaval shunts (1, 2) and urease treatment (3). These approaches are not ideal for studies on hyperammonemia. Shunting techniques are complicated and require skillful surgery. Moreover, the animals develop secondary effects, which obscure the effects due to hyperammonemia per se. Urease treatment is time consuming and not suitable for long-term studies.
The aim of this work was to develop and characterize a simple, nontraumatic model useful for long-term studies of hyperammonemia. We report here a new model consisting of feeding rats a diet containing ammonium acetate (20% w/w). Rats were maintained on this diet for up t o 100 days without untoward manifestations. As an initial characterization of the model, we have studied some aspects of nitrogen metabolism including ammonia, urea and amino acid levels as well as the activities of some key enzymes. Ammonia levels in blood increased =3-fold, whereas in brain, liver and muscle the increases were 36, 34 and 50%, respectively. This model could be