Glyoxal is an interesting endogenous α-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 LD50 of glyoxal towards isolated rat hepatocytes was 5 mM. However, 10 μM glyoxal was sufficient to overcome hepatocyte resistance to H2O2-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 H2O2-induced oxidative stress and glyoxal which involves an inhibition of the NADPH supply by glyoxal resulting in cytotoxicity caused by H2O2-induced mitochondrial oxidative stress.