Effects of alpha-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by d-amphetamine.
Previous studies have shown that treatment with free radical scavengers attenuated the D-amphetamine (AMPH) neurotoxicity. But several of these agents also prevent AMPH-induced elevation of body temperature in the rat. Thus, further studies are needed to determine if blockade of the production of free radical or hypothermia are related to the neuroprotective mechanism of the free radical scavengers for AMPH neurotoxicity. In the present study, we examined the effects of the free radical scavengers alpha-phenyl-N-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC) on long-term depletion of striatal dopamine (DA) and lipid peroxidation formation and on hyperthermia induced by AMPH. We also determined their effects on acute hydroxyl radical formation after direct intrastriatal infusion of AMPH. The results showed that both significantly attenuated long-term DA depletion and lipid peroxidation formation in the rat striatum at the dose range that did not block hyperthermia induced by AMPH. These agents also completely inhibited the production of hydroxyl radical after AMPH infusion into the striatum. Our results suggest that free radical scavengers such as PBN and NAC could protect against AMPH-induced oxidative stress and DAergic terminal toxicity via their free radical removing property independent of lowering the core body temperature of rats, and imply that supplement with antioxidants is a potential strategy in the treatment of AMPH neurotoxicity.
Wan
Fang-Jung
FJ
Graduate Institute of Undersea Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
Tung
Che-Se
CS
Shiah
I-Shin
IS
Lin
Hui-Ching
HC
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003497:Cyclic N-Oxides; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley
D003497:Cyclic N-Oxides; D018765:Dopamine Uptake Inhibitors; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D017665:Hydroxyl Radical; C029217:phenyl-N-tert-butylnitrone; C009135:2,3-dihydroxybenzoic acid; D003913:Dextroamphetamine; D004298:Dopamine; D000111:Acetylcysteine