PMID- 24819089
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20140611
IS  - 1559-0720 (Electronic)
IS  - 0163-4984 (Linking)
VI  - 159
IP  - 1-3
DP  - 2014 Jun
TI  - Preventive effects of dextromethorphan on methylmercury-induced glutamate 
      dyshomeostasis and oxidative damage in rat cerebral cortex.
PG  - 332-45
LID - 10.1007/s12011-014-9977-8 [doi]
AB  - Methylmercury (MeHg) is a well-known environmental pollutant leading to 
      neurotoxicant associated with aberrant central nervous system (CNS) functions, 
      but its toxic mechanisms have not yet been fully recognized. In the present 
      study, we tested the hypothesis that MeHg induces neuronal injury via glutamate 
      (Glu) dyshomeostasis and oxidative damage mechanisms and that these effects are 
      attenuated by dextromethorphan (DM), a low-affinity and noncompetitive 
      N-methyl-D-aspartate receptor (NMDAR) antagonist. Seventy-two rats were randomly 
      divided into four groups of 18 animals in each group: control group, MeHg-treated 
      group (4 and 12 mumol/kg), and DM-pretreated group. After the 4-week treatment, we 
      observed that the administration of MeHg at a dose of 12 mumol/kg significantly 
      increased in total mercury (Hg) levels, disrupted Glu metabolism, overexcited 
      NMDARs, and led to intracellular calcium overload in the cerebral cortex. We also 
      found that MeHg reduced nonenzymatic and enzymatic antioxidants, enhanced 
      neurocyte apoptosis, induced reactive oxygen species (ROS), and caused lipid, 
      protein, and DNA peroxidative damage in the cerebral cortex. Moreover, 
      glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) 
      appeared to be inhibited by MeHg exposure. These alterations were significantly 
      prevented by the pretreatment with DM at a dose of 13.5 mumol/kg. In conclusion, 
      these findings strongly implicate that DM has potential to protect the brain from 
      Glu dyshomeostasis and oxidative damage resulting from MeHg-induced neurotoxicity 
      in rat.
FAU - Feng, Shu
AU  - Feng S
AD  - Department of Environmental Health, School of Public Health, China Medical 
      University, Shenyang, People's Republic of China.
FAU - Xu, Zhaofa
AU  - Xu Z
FAU - Liu, Wei
AU  - Liu W
FAU - Li, Yuehui
AU  - Li Y
FAU - Deng, Yu
AU  - Deng Y
FAU - Xu, Bin
AU  - Xu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140513
PL  - United States
TA  - Biol Trace Elem Res
JT  - Biological trace element research
JID - 7911509
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Methylmercury Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - RWZ4L3O1X0 (methylmercuric chloride)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/*drug effects/*metabolism
MH  - Dextromethorphan/*pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Female
MH  - Glutamic Acid/*metabolism
MH  - Male
MH  - Methylmercury Compounds/*toxicity
MH  - Oxidation-Reduction/drug effects
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
EDAT- 2014/05/14 06:00
MHDA- 2015/01/27 06:00
CRDT- 2014/05/14 06:00
PHST- 2014/01/25 00:00 [received]
PHST- 2014/04/10 00:00 [accepted]
PHST- 2014/05/14 06:00 [entrez]
PHST- 2014/05/14 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
AID - 10.1007/s12011-014-9977-8 [doi]
PST - ppublish
SO  - Biol Trace Elem Res. 2014 Jun;159(1-3):332-45. doi: 10.1007/s12011-014-9977-8. 
      Epub 2014 May 13.