In vivo trapping of nitric oxide in the brain of neonatal rats treated with the HIV-1 envelope protein gp 120: protective effects of alpha-phenyl-tert-butylnitrone.
AIDS dementia complex is a neurological syndrome characterized by cognitive deficits and motor and behavioral dysfunction. The HIV-1 envelope glycoprotein gp 120 has been implicated in the development of AIDS dementia. This protein has been shown to be neurotoxic and to cause learning impairment and retardation of the development of complex motor behavior in rat neonates. Nitric oxide has been implicated in gp 120-induced neurotoxicity. In the present study, we report for the first time in vivo evidence for the formation of nitric oxide in the CNS as a result of multiple subcutaneous injections of gp 120 to neonatal rats. Nitric oxide was trapped in the brain of neonatal rats by N-methyl-D-glucamine dithiocarbamate-Fe and the nitric oxide content measured by electron paramagnetic resonance spectroscopy. The nitrone-based spin trap alpha-phenyl-tert-butylnitrone at 50 mg/kg was found to prevent gp 120-mediated nitric oxide formation and to also protect against gp 120-induced behavioral impairment.
Tabatabaie
T
T
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA.
Stewart
C
C
Pye
Q
Q
Kotake
Y
Y
Floyd
R A
RA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003497:Cyclic N-Oxides; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003497:Cyclic N-Oxides; D015699:HIV Envelope Protein gp120; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C029217:phenyl-N-tert-butylnitrone