Document Detail


The cytotoxic mechanism of glyoxal involves oxidative stress.
MedLine Citation:
PMID:  15345333     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glyoxal is a reactive alpha-oxoaldehyde that is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose and degradation of glycated proteins. Glyoxal is capable of inducing cellular damage, like methylglyoxal (MG), but may also accelerate the rate of glycation leading to the formation of advanced glycation end-products (AGEs). However, the mechanism of glyoxal cytotoxicity has not been precisely defined. In this study we have focused on the cytotoxic effects of glyoxal and its ability to overcome cellular resistance to oxidative stress. Isolated rat hepatocytes were incubated with different concentrations of glyoxal. Glyoxal by itself was cytotoxic at 5mM, depleted GSH, formed reactive oxygen species (ROS) and collapsed the mitochondrial membrane potential. Glyoxal also induced lipid peroxidation and formaldehyde formation. Glycolytic substrates, e.g. fructose, sorbitol and xylitol inhibited glyoxal-induced cytotoxicity and prevented the decrease in mitochondrial membrane potential suggesting that mitochondrial toxicity contributed to the cytotoxic mechanism. Glyoxal cytotoxicity was prevented by the glyoxal traps d-penicillamine or aminoguanidine or ROS scavengers were also cytoprotective even when added some time after glyoxal suggesting that oxidative stress contributed to the glyoxal cytotoxic mechanism.
Authors:
Nandita Shangari; Peter J O'Brien
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  68     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-03     Completed Date:  2004-11-03     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1433-42     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ont., Canada M5S 2S2.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival / drug effects
Cells, Cultured
Cytosol / drug effects,  enzymology
Glutathione / metabolism
Glutathione Disulfide / metabolism
Glutathione Reductase / metabolism
Glyoxal / antagonists & inhibitors,  pharmacology*
Hepatocytes / drug effects*,  metabolism
Lipid Peroxidation / drug effects*
Male
Membrane Potentials / drug effects
Mitochondria / drug effects,  physiology
Oxidative Stress / drug effects*,  physiology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 107-22-2/Glyoxal; 27025-41-8/Glutathione Disulfide; 70-18-8/Glutathione; EC 1.8.1.7/Glutathione Reductase

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


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