Acetaldehyde does not inhibit glutathione peroxidase and glutathione reductase from mouse liver in vitro.
Acetaldehyde, the primary ethanol metabolite, has been implicated in the pathogenesis of alcoholic liver disease, but the mechanism involved is still under investigation. This study aims at the search for direct in vitro effects of different concentrations of acetaldehyde (30, 100 and 300microM) on the activities of glutathione reductase (GR), glutathione peroxidase (GPx) from liver supernatants, and the thiol-peroxidase activity of ebselen. They did not change after pre-incubation with acetaldehyde, which suggests that acetaldehyde does not have any direct effect. Nor were direct effects of acetaldehyde toward thiols, such as dithioerythritol and glutathione (GSH), observed either, even though GSH - measured as non-protein thiols from liver supernatants - were oxidized in the presence of acetaldehyde. In addition, acetaldehyde (up to 300microM) significantly oxidized GSH when incubated in the presence of commercially available gamma-glutamyltranspeptidase (GGT), but not in the presence of glutathione-S-transferase. The interaction between ebselen and GSH was also evaluated in an attempt to better understand the possible link between acetaldehyde and nucleophilic selenol groups. The formation and stability of ebselen intermediaries, produced in the chemical interaction between GSH and ebselen, were not affected by acetaldehyde either. Overall, the acetaldehyde oxidation of hepatic low-molecular thiols depends on mouse liver constituents and GGT is proposed as an important enzyme involved in this phenomenon. Thiol depletion, a phenomenon usually observed in the livers of alcoholic patients, can be related to GSH metabolism, and the involvement of GGT may reflect a molecular mechanism involved in thiol oxidation.
Pivetta
Lucinéia A
LA
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
Dafre
Alcir L
AL
Zeni
Gilson
G
Rocha
João B T
JB
Farina
Marcelo
M
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D013057:Spectrum Analysis
D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D000079:Acetaldehyde