Glyoxal markedly compromises hepatocyte resistance to hydrogen peroxide.
Glyoxal is an interesting endogenous alpha-oxoaldehyde as it originates from pathways that have been linked to various pathologies, including lipid peroxidation, DNA oxidation and glucose autoxidation. In our previous study we showed that the LD(50) of glyoxal towards isolated rat hepatocytes was 5mM. However, 10microM glyoxal was sufficient to overcome hepatocyte resistance to H(2)O(2)-mediated cytotoxicity. Hepatocyte GSH oxidation, NADPH oxidation, reactive oxygen species formation, DNA oxidation, protein carbonylation and loss of mitochondrial potential were also markedly increased before cytotoxicity ensued. Cytotoxicity was prevented by glyoxal traps, the ferric chelator, desferoxamine, and antioxidants such as quercetin and propyl gallate. These results suggest there is a powerful relationship between H(2)O(2)-induced oxidative stress and glyoxal which involves an inhibition of the NADPH supply by glyoxal resulting in cytotoxicity caused by H(2)O(2)-induced mitochondrial oxidative stress.
Department of Pharmaceutical Sciences, University of Toronto, 19 Russell St, Toronto, Ont., Canada M5S 2S2.
Nandita
N
Shangari
Tom S
TS
Chan
Marija
M
Popovic
Peter J
PJ
O'Brien
D000818:Animals; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006037:Glyoxal / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D006037:Glyoxal; D009249:NADP; D006861:Hydrogen Peroxide; D005978:Glutathione