Lithium protection against oxygen toxicity in rats: ammonia and amino acid metabolism

1. The use of Li pre-treatment in rats before high pressure oxygen exposure has been reported effective in controlling convulsions. This is an effect which is better demonstrated if exposure to oxygen follows shortly after Li injection than exposure following several hours later. 2. This study has investigated the hypothesis that the protective action of Li may be exerted, in the short term, by its removing ammonia from the blood and alleviating the latter's known toxic action. 3. A normal Li distribution time profile in unstressed rat brain and blood following intraperitoneal injection has been established. Brain and blood ammonia, amino acids and Li concentrations were also measured in Li-treated animals exposed and convulsed by oxygen. These measurements were made both shortly (15 min) and also several hours after (24 hr) Li treatment. Ammonia and amino acid values in Li-protected groups were compared to normal unstressed animal values and also to values in animals convulsed by oxygen unprotected by Li pre-treatment. 4. In rat brain abd blood significant (P less than 0-001) elevation of ammonia and glutamine and depression of gamma-amino butyric acid (brain only) and glutamate was noted following oxygen treatment in unprotected animals. Prior injection of Li 15 min before high pressure oxygen exposure delayed convulsions twice as long. Additionally if these animals were only exposed to oxygen for a period of time equal to that which would normally produce convulsions in unprotected animals, brain and blood ammonia and amino acids were maintained near to unstressed animal levels. Concomitantly, blood Li concentrations were considerably depressed below the values one would expect from the previously determined Li distribution time profile. 5. In rats exposed to high pressure oxygen 24 hr after Li treatment there was no protective action against high pressure oxygen convulsion, rather a potentiating effect for convulsion was seen. 6. These data present compelling evidence for the controlling effect of Li in rats, on rising blood ammonia concentration which occurs in high pressure oxygen exposure. The effect might well be due to the known chelating properties of Li with ammonia.