PMID- 26804444
OWN - NLM
STAT- MEDLINE
DCOM- 20170109
LR  - 20170110
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 95
DP  - 2016 May
TI  - Creatine affords protection against glutamate-induced nitrosative and oxidative 
      stress.
PG  - 4-14
LID - S0197-0186(16)30002-X [pii]
LID - 10.1016/j.neuint.2016.01.002 [doi]
AB  - Creatine has been reported to exert beneficial effects in several 
      neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative 
      stress play an etiological role. The purpose of this study was to investigate the 
      protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) 
      receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide 
      (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to 
      glutamate (60-80 mM) or H2O2 (200-300 muM) for 24 h decreased cellular viability 
      and increased dichlorofluorescein (DCF) fluorescence (indicative of increased 
      reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by 
      mono-nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 muM) 
      reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine 
      against glutamate-induced toxicity involves its antioxidant effect, since 
      creatine, similar to MK-801, prevented the increase on DCF fluorescence induced 
      by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and 
      H2O2-induced increases in NOx levels. In another set of experiments, the 
      repeated, but not acute, administration of creatine (300 mg/kg, po) in mice 
      prevented the decreases on cellular viability and mitochondrial membrane 
      potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of 
      hippocampal slices incubated with glutamate (10 mM). Creatine 
      concentration-dependent decreased the amount of nitrite formed in the reaction of 
      oxygen with NO produced from sodium nitroprusside solution, suggesting that its 
      protective effect against glutamate or H2O2-induced toxicity might be due to its 
      scavenger activity. Overall, the results suggest that creatine may be useful as 
      adjuvant therapy for neurodegenerative disease treatments.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Cunha, Mauricio P
AU  - Cunha MP
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil. Electronic address: mauricio.personal@gmail.com.
FAU - Lieberknecht, Vicente
AU  - Lieberknecht V
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Ramos-Hryb, Ana Belen
AU  - Ramos-Hryb AB
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Olescowicz, Gislaine
AU  - Olescowicz G
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Ludka, Fabiana K
AU  - Ludka FK
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Tasca, Carla I
AU  - Tasca CI
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Gabilan, Nelson H
AU  - Gabilan NH
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
FAU - Rodrigues, Ana Lucia S
AU  - Rodrigues AL
AD  - Department of Biochemistry, Center of Biological Sciences, Universidade Federal 
      de Santa Catarina, Campus Universitario, Trindade, 88040-900, Florianopolis, SC, 
      Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160119
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Creatine/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glutamic Acid/*toxicity
MH  - Hippocampus/*drug effects/metabolism
MH  - Humans
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitrosation/drug effects/physiology
MH  - Organ Culture Techniques
MH  - Oxidative Stress/*drug effects/physiology
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Cellular viability
OT  - Creatine
OT  - Glutamate
OT  - Hydrogen peroxide
OT  - Nitric oxide
EDAT- 2016/01/26 06:00
MHDA- 2017/01/10 06:00
CRDT- 2016/01/26 06:00
PHST- 2015/04/01 00:00 [received]
PHST- 2016/01/07 00:00 [revised]
PHST- 2016/01/18 00:00 [accepted]
PHST- 2016/01/26 06:00 [entrez]
PHST- 2016/01/26 06:00 [pubmed]
PHST- 2017/01/10 06:00 [medline]
AID - S0197-0186(16)30002-X [pii]
AID - 10.1016/j.neuint.2016.01.002 [doi]
PST - ppublish
SO  - Neurochem Int. 2016 May;95:4-14. doi: 10.1016/j.neuint.2016.01.002. Epub 2016 Jan 
      19.