PMID- 12899943
OWN - NLM
STAT- MEDLINE
DCOM- 20040810
LR  - 20190827
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 35
IP  - 4
DP  - 2003 Aug 15
TI  - Copper blocks quinolinic acid neurotoxicity in rats: contribution of antioxidant 
      systems.
PG  - 418-27
AB  - Reactive oxygen species and oxidative stress are involved in quinolinic acid 
      (QUIN)-induced neurotoxicity. QUIN, a N-methyl-D-aspartate receptor (NMDAr) 
      agonist and prooxidant molecule, produces NMDAr overactivation, excitotoxic 
      events, and direct reactive oxygen species formation. Copper is an essential 
      metal exhibiting both modulatory effects on neuronal excitatory activity and 
      antioxidant properties. To investigate whether this metal is able to counteract 
      the neurotoxic and oxidative actions of QUIN, we administered copper (as CuSO(4)) 
      intraperitoneally to rats (2.5, 5.0, 7.5, and 10.0 mg/kg) 30 min before the 
      striatal infusion of 1 microliter of QUIN (240 nmol). A 5.0 mg/kg CuSO(4) dose 
      significantly increased the copper content in the striatum, reduced the 
      neurotoxicity measured both as circling behavior and striatal gamma-aminobutyric 
      acid (GABA) depletion, and blocked the oxidative injury evaluated as striatal 
      lipid peroxidation (LP). In addition, copper reduced the QUIN-induced decreased 
      striatal activity of Cu,Zn-dependent superoxide dismutase, and increased the 
      ferroxidase activity of ceruloplasmin in cerebrospinal fluid from QUIN-treated 
      rats. However, copper also produced significant increases of plasma lactate 
      dehydrogenase activity and mortality at the highest doses employed (7.5 and 10.0 
      mg/kg). These results show that at low doses, copper exerts a protective effect 
      on in vivo QUIN neurotoxicity.
FAU - Santamaria, Abel
AU  - Santamaria A
AD  - Laboratorio de Aminoacidos Excitadores/Departamento de Neuroquimica, Instituto 
      Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico, D.F., 
      Mexico.
FAU - Flores-Escartin, Abigail
AU  - Flores-Escartin A
FAU - Martinez, Juan Carlos
AU  - Martinez JC
FAU - Osorio, Laura
AU  - Osorio L
FAU - Galvan-Arzate, Sonia
AU  - Galvan-Arzate S
FAU - Pedraza-Chaverri, Jose
AU  - Pedraza-Chaverri J
FAU - Maldonado, Perla D
AU  - Maldonado PD
FAU - Medina-Campos, Omar N
AU  - Medina-Campos ON
FAU - Jimenez-Capdeville, Maria E
AU  - Jimenez-Capdeville ME
FAU - Manjarrez, Joaquin
AU  - Manjarrez J
FAU - Rios, Camilo
AU  - Rios C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antioxidants)
RN  - 0 (Free Radicals)
RN  - 0 (Ions)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 789U1901C5 (Copper)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.16.3.1 (Ceruloplasmin)
RN  - F6F0HK1URN (Quinolinic Acid)
RN  - LRX7AJ16DT (Copper Sulfate)
SB  - IM
EIN - Free Radic Biol Med. 2004 Jul 15;37(2):284. Chaverri, Jose Pedraza [corrected to 
      Pedraza-Chaverri, Jose]
MH  - Animals
MH  - Antioxidants/metabolism/*pharmacology
MH  - Blotting, Western
MH  - Body Weight
MH  - Ceruloplasmin/metabolism
MH  - Copper/*metabolism
MH  - Copper Sulfate/metabolism
MH  - Free Radicals
MH  - Ions
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipid Peroxidation
MH  - Male
MH  - Oxidative Stress
MH  - Quinolinic Acid/*metabolism/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species
MH  - Receptors, N-Methyl-D-Aspartate/agonists
MH  - Superoxide Dismutase/metabolism
MH  - Time Factors
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2003/08/06 05:00
MHDA- 2004/08/11 05:00
CRDT- 2003/08/06 05:00
PHST- 2003/08/06 05:00 [pubmed]
PHST- 2004/08/11 05:00 [medline]
PHST- 2003/08/06 05:00 [entrez]
AID - S0891584903003174 [pii]
AID - 10.1016/s0891-5849(03)00317-4 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2003 Aug 15;35(4):418-27. doi: 
      10.1016/s0891-5849(03)00317-4.