PMID- 12835115
OWN - NLM
STAT- MEDLINE
DCOM- 20030923
LR  - 20230320
IS  - 1029-8428 (Print)
IS  - 1029-8428 (Linking)
VI  - 5
IP  - 4
DP  - 2003
TI  - Homocysteine-induced brain lipid peroxidation: effects of NMDA receptor blockade, 
      antioxidant treatment, and nitric oxide synthase inhibition.
PG  - 237-43
AB  - The effect of homocysteine (HCY) on lipid peroxidation (LP), a current mechanism 
      of oxidative neurotoxicity, was investigated in rat brain synaptosomes. LP was 
      assessed by measuring the amount of thiobarbituric acid-reactive substances 
      (TBARS) formed from synaptosomal fractions following HCY treatment. Increasing 
      HCY concentrations (5-1000 micro M) enhanced the TBARS formation in brain 
      synaptosomes in a concentration-dependent manner. When compared at equimolar 
      concentrations (100 micro M), the oxidative potency of HCY was lower than that of 
      the oxidant ferrous sulfate, similar to that produced by glutamate (Glu) and the 
      mitochondrial toxin 3-nitropropionic acid, and higher than that of the Glu 
      agonists, kainate and quinolinate. The N-methyl-D-aspartate receptor (NMDAr) 
      antagonist dizocilpine (MK-801) completely blocked the HCY-induced LP at 
      concentrations between 5 to 1000 micro M, whereas the well-known antioxidant 
      N-acetylcysteine (NAC) was less effective, but still protective against the HCY 
      oxidative toxicity at higher concentrations (400 and 1000 micro M). Three nitric 
      oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), Nomega-nitro-L-arginine 
      (L-NARG) and Nomega-nitro-L-arginine methyl ester (L-NAME), were also tested on 
      HCY-induced LP at increasing concentrations. Both nonspecific NOS inhibitors 
      (L-NARG and L-NAME) decreased more effectively the HCY-induced LP than did the 
      selective neuronal NOS inhibitor, 7-NI. These results show that submillimolar 
      concentrations of HCY can induce oxidative injury to nerve terminals, and this 
      effect involves NMDAr stimulation, NOS activation, and associated free radicals 
      formation.
FAU - Jara-Prado, Aurelio
AU  - Jara-Prado A
AD  - Departamento de Genetica, Instituto Nacional de Neurologia y Neurocirugia Manuel 
      Velasco Suarez, S.S.A. Insurgentes Sur # 3877, Mexico D.F., 14269, Mexico.
FAU - Ortega-Vazquez, Alberto
AU  - Ortega-Vazquez A
FAU - Martinez-Ruano, Leticia
AU  - Martinez-Ruano L
FAU - Rios, Camilo
AU  - Rios C
FAU - Santamaria, Abel
AU  - Santamaria A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Antioxidants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Indazoles)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 2149-70-4 (Nitroarginine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - UX0N37CMVH (7-nitroindazole)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Brain/*metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Free Radical Scavengers/pharmacology
MH  - Homocysteine/metabolism/*toxicity
MH  - Indazoles/pharmacology
MH  - Lipid Peroxidation/drug effects/physiology
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors/metabolism
MH  - Nitroarginine/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - Thiobarbituric Acid Reactive Substances/metabolism
EDAT- 2003/07/02 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - 10.1007/BF03033381 [doi]
PST - ppublish
SO  - Neurotox Res. 2003;5(4):237-43. doi: 10.1007/BF03033381.