PMID- 23498342
OWN - NLM
STAT- MEDLINE
DCOM- 20131001
LR  - 20131121
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 183
IP  - 2
DP  - 2013 Aug
TI  - Effect of modulating the allosteric sites of N-methyl-D-aspartate receptors in 
      ischemia-reperfusion induced acute kidney injury.
PG  - 668-77
LID - S0022-4804(13)00064-4 [pii]
LID - 10.1016/j.jss.2013.01.040 [doi]
AB  - BACKGROUND: Acute kidney injury (AKI) is one of the major health problems in 
      developed as well as developing countries. The literature regarding the role of 
      N-methyl-D-aspartate receptors (NMDAR) and the impact of the modulation of its 
      allosteric sites on renal function is inadequate. The present study investigated 
      the effect of modulating allosteric sites of NMDAR in 
      ischemia-reperfusion-induced AKI. MATERIALS AND METHODS: We subjected rats to 
      bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce 
      AKI. We measured blood urea nitrogen, serum creatinine, uric acid, and lactate 
      dehydrogenase to assess kidney injury. We assayed the thiobarbituric 
      acid-reactive substances, reduced glutathione level, and myeloperoxidase and 
      catalase activity to assess oxidative stress in renal tissue, and used 
      hematoxylin-eosin staining to observe histopathologic changes. RESULTS: 
      Ischemia-reperfusion induced AKI, as demonstrated by an increase in serum 
      parameters, oxidative stress and histopathologic changes in renal tissue. The 
      NMDA agonist glutamic acid and polyamine binding site agonist spermidine 
      significantly aggravated oxidative stress and ischemia-reperfusion-induced AKI. 
      Various NMDA receptor antagonists, including glycine binding site inhibitor 
      kynurenic acid, polyamine binding site inhibitor ketamine, and channel blocking 
      agent magnesium sulfate, attenuated ischemia-reperfusion-induced AKI and 
      significantly reduced oxidative stress, which suggests a role for NMDA receptors 
      and the importance of regulating its allosteric sites in AKI. CONCLUSIONS: Acute 
      kidney injury is associated with the activation of NMDA receptors, as well as 
      significant oxidative stress. The antagonism of various allosteric sites of NMDA 
      receptors affords significant benefit against ischemia-reperfusion-induced AKI.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Pundir, Mandeep
AU  - Pundir M
AD  - Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 
      India.
FAU - Arora, Shiyana
AU  - Arora S
FAU - Kaur, Tajpreet
AU  - Kaur T
FAU - Singh, Randhir
AU  - Singh R
FAU - Singh, Amrit Pal
AU  - Singh AP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130210
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 11062-77-4 (Superoxides)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 690G0D6V8H (Ketamine)
RN  - 7487-88-9 (Magnesium Sulfate)
RN  - EC 1.11.1.6 (Catalase)
RN  - GAN16C9B8O (Glutathione)
RN  - H030S2S85J (Kynurenic Acid)
RN  - U87FK77H25 (Spermidine)
SB  - IM
MH  - Acute Kidney Injury/*etiology/metabolism/*physiopathology
MH  - Allosteric Site/drug effects/*physiology
MH  - Animals
MH  - Catalase/metabolism
MH  - Glutamic Acid/pharmacology
MH  - Glutathione/metabolism
MH  - Ketamine/pharmacology
MH  - Kynurenic Acid/pharmacology
MH  - Magnesium Sulfate/pharmacology
MH  - Male
MH  - Models, Animal
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*physiology
MH  - Reperfusion Injury/*complications
MH  - Spermidine/pharmacology
MH  - Superoxides/metabolism
MH  - Thiobarbituric Acid Reactive Substances/metabolism
OTO - NOTNLM
OT  - Allosteric modulation
OT  - Ischemia-reperfusion
OT  - Kidney injury
OT  - NMDA
EDAT- 2013/03/19 06:00
MHDA- 2013/10/18 06:00
CRDT- 2013/03/19 06:00
PHST- 2012/09/20 00:00 [received]
PHST- 2012/12/28 00:00 [revised]
PHST- 2013/01/18 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
AID - S0022-4804(13)00064-4 [pii]
AID - 10.1016/j.jss.2013.01.040 [doi]
PST - ppublish
SO  - J Surg Res. 2013 Aug;183(2):668-77. doi: 10.1016/j.jss.2013.01.040. Epub 2013 Feb 
      10.