Comparison of the Effects of Ammonia on Brain Mitochondrial Function in Rats and Gulf Toadfish (Opsanus beta)

We compared the effect of hyperammonemia on NADH levels in brain slices, and on the rate of oxygen consumption from isolated non-synaptic brain mitochondria, in ammoniasensitive Wistar rats with that in ammonia-tolerant gulf toadfish (Opsanus beta). The NADH content was significantly decreased (12% less than control after 45 min with 1 mM NH4Cl) in rat brain slices, but it was not affected in brain slices from toadfish (with both 1 mM and 6 mM NH4Cl). The rates of oxygen consumption of different sets of enzymes of the electron transport chain (ETC; complexes I,II,III, and IV; II,III, and IV; and IV alone) were unaltered by hyperammonemic conditions in isolated non-synaptic mitochondria from either rats or toadfish. These results lead us to conclude that the differing effects of ammonia on NADH levels in rat and toadfish brain slices must be due to aspects other than the direct effects of ammonia on enzymes of the ETC. Additionally, since these effects were seen in vitro, our studies have enabled us to rule out the possibility that effects of ammonia on metabolism were via indirect systemic effects. These results are discussed in the context of current views on mechanisms of CNS damage in hyperammonemic states.