Document Detail


Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices.
MedLine Citation:
PMID:  17893460     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Exogenous pyruvate and ethyl pyruvate (EP), the key ingredient in a new Ringer's solution in clinical trials, are antioxidants as well as metabolic substrates. In vivo studies show both to be protective in oxidative stress, with EP being better. The authors used an acute rat brain slice preparation to compare EP and pyruvate rescue after H(2)O(2) oxidative stress, asking whether EP was again better and whether its actions were exclusively metabolic.
METHODS: Oxygenated neonatal P7 cerebrocortical slices were exposed for 1 h to 2 mM H(2)O(2), and recovered for 4 h with artificial cerebrospinal fluid having 2 mM glucose and (1) 20 mM EP, (2) 20 mM pyruvate, or (3) 1 mM of the nonmetabolizable radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN). Perchloric acid extracts were studied with 31P/1H nuclear magnetic resonance at 14.1 T. Acute cell injury was assessed by counting terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL)-stained cells.
RESULTS: At the end of recovery, preservation of adenosine triphosphate and N-acetylaspartate was better with EP than with pyruvate. Adenosine triphosphate preservation was best when PBN and EP were coadministered. 1H nuclear magnetic resonance revealed changes in lactate, alanine, gamma-aminobutyric acid, glutamate, glutamine, succinate, taurine, and myoinositol. Two-dimensional [1H-13C] heteronuclear single quantum coherence spectroscopy found that 13C-EP administration produced the same tricarboxylic acid metabolites as C-pyruvate. TUNEL-positive cell percentages with EP were less than half of those for PBN or pyruvate rescue (P < 0.05).
CONCLUSION: EP enters cells, provides pyruvate as a tricarboxylic acid substrate, and is more protective. Although EP provides metabolic protection of adenosine triphosphate levels, it does not maximize antioxidant protection.
Authors:
Jianying Zeng; Jia Liu; Guo-Yuan Yang; Mark J S Kelly; Thomas L James; Lawrence Litt
Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  107     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-25     Completed Date:  2007-10-29     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-40     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia and Perioperative Care, The University of California, San Francisco, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Animals, Newborn / physiology*
Antioxidants / pharmacology
Aspartic Acid / analogs & derivatives,  metabolism
Cell Count
Cerebral Cortex / drug effects*,  metabolism*
Citric Acid Cycle / drug effects
Cyclic N-Oxides / pharmacology
DNA Fragmentation / drug effects
Free Radical Scavengers / pharmacology
In Situ Nick-End Labeling
Magnetic Resonance Spectroscopy
Neuroprotective Agents*
Oxidative Stress / drug effects*
Perchloric Acid / metabolism
Pyruvates / pharmacology*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
GM34767/GM/NIGMS NIH HHS; R01 GM034767-20/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Neuroprotective Agents; 0/Pyruvates; 3376-24-7/phenyl-N-tert-butylnitrone; 56-65-5/Adenosine Triphosphate; 56-84-8/Aspartic Acid; 617-35-6/ethyl pyruvate; 7601-90-3/Perchloric Acid; 997-55-7/N-acetylaspartate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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