Recent studies have implicated
nitric oxide (NO*) as a mediator of CNS hyperbaric O2 (HBO2) toxicity. One mechanism by which NO* may contribute to HBO2-induced brain toxicity involves a neurotoxic, pro-oxidative action of NO* via the formation of the potent
oxidant peroxynitrite (ONOO-). The present study compares: (a) the formation of
protein nitrotyrosine as a marker of ONOO- accumulation and (b)
protein oxidation as an
indicator of
reactive oxygen species production during HBO2 exposure. Rats were exposed to 5 atm 100% O2 to pre-convulsive exposure or until the occurrence of electroencephalographic (EEG)
seizures. After exposures, brains were analyzed for
protein nitrotyrosine (NT) and
protein carbonyl measurement by Western blot and for
superoxide dismutase (SOD) activity by NBT assay. The results show a significant increase in
protein NT, exceeding control level by several fold. There was only a slow and non-significant increase in the quantity of oxidized
proteins during the pre-convulsive phase of HBO2 exposure. Levels of both
protein NT and
protein carbonyls were significantly (p<0.05) elevated after
seizures. Total SOD activity was not changed during preconvulsive exposures, but was significantly (p<0.05) elevated post-
seizures. The specific
neuronal nitric oxide synthase (NOS) inhibitor,
7-nitroindazole (7-NI), significantly reduced the increases in seizure-induced
protein NT and
protein carbonyl and at the same time very effectively (p<0.05) delayed onset of HBO2
seizures. Pre-seizure increases in
protein NT might indicate its role in the mechanism of HBO2-induced brain toxicity. This is supported by the observed capacity of 7-NI to inhibit
tyrosine nitration and increase time to seizure.