Vol. 283, Issue 3, R598-R603, September 2002
Comparison of the effects of ammonia on brain mitochondrial
function in rats and gulf toadfish
Clémence M.
Veauvy1,
Yuxiang
Wang1,2,
Patrick J.
Walsh1, and
Miguel A.
Pérez-Pinzón1,3
1 National Institute of Environmental Health
Sciences Marine and Freshwater Biomedical Science Center, Division
of Marine Biology and Fisheries, Rosenstiel School of Marine and
Atmospheric Science, University of Miami 33149;
3 Department of Neurology and Neuroscience, School
of Medicine, University of Miami, Miami, Florida 33131; and
2 Department of Biology, Queen's University, Kingston,
Ontario, K7L 3N6 Canada
We compared the effect of hyperammonemia
on NADH levels in brain slices and on the rate of oxygen consumption
from isolated nonsynaptic brain mitochondria in ammonia-sensitive
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 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 nonsynaptic
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, because these
effects were seen in vitro, our studies 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 central nervous system damage in hyperammonemic states.
hepatic encephalopathy; hyperammonemia; NADH; mitochondria; Opsanus beta; glutamine metabolism
