Early neuroprotective effect of nitric oxide in developing rat brain irradiated in utero.
Pregnant Wistar rats were exposed on day 17 of gestation to 1 Gy gamma irradiation from a Co(60) source. Even though it is established that gamma radiation-dependent damage is mainly due to free radical generation neither the ascorbyl radical/ascorbate ratio nor the lipid radical content in developing rat brain were affected by prenatal irradiation. A distinctive EPR signal for the adduct NO-Fe-MGD (g=2.03 and a(N)=12.5 G) was detected in brain homogenates prepared from irradiated rats. Nitric oxide (NO)-dependent EPR signal increased in a time-dependent manner up to 2h post-irradiation. NO concentration in unirradiated brains was 37+/-4 pmol/g brain and 45+/-2, 77+/-5 and 216+/-6 after 30, 60 and 120 min post-irradiation, respectively. Total nitric oxide synthase activity was increased by 77 and 51% after 30 and 60 min post-irradiation, respectively, and returned to control values after 120 min. Thus, increased NO steady-state concentration could be ascribed to an increase in NOS activity. Taken as a whole, these results suggest that NO might act to protect the developing brain from the cytotoxicity of reactive species.
Gisone
Pablo
P
Laboratorio de Radiopatología, Autoridad Regulatoria Nuclear, Buenos Aires, Argentina. pgisone@cae.arn.gov.ar
Boveris
Alejandro D
AD
Dubner
Diana
D
Perez
María Rosario
MR
Robello
Elizabeth
E
Puntarulo
Susana
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000528:radiation effects*; D001923:Brain Chemistry / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000199:Actins; D005609:Free Radicals; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D001205:Ascorbic Acid