A liver nuclear ethanol metabolizing system. Formation of metabolites that bind covalently to macromolecules and lipids

MI DÍAZ GÓMEZ; SL FANELLI; GD CASTRO; MI DÍAZ GÓMEZ, SL FANELLI, GD CASTRO, MH COSTANTINI Y JA CASTRO.; JA CASTRO

TOXICOLOGY

Elsevier science Irland Ltd

Lugar: Irlanda; Año: 1999 vol. 138 p. 19 - 28

0300-483X

Recent studies from the laboratory reported the presence in highly purified liver nuclear preparations free of   endoplasmic reticulum, mitocondria or cytosol, of an ethanol metabolizing group of enzymes (NEMS) leading to   acetaldehyde and to hydroxyl and 1-hydroxyethyl (1HEt) free radicals. In the present study it is reported that when   NEMS metabolize [14C]ethanol using NADPH as cofactor, its reactive metabolites bind covalently to nuclear proteins    and lipids. No covalent binding to DNA was detected with presently used procedures. The covalent binding to   nuclear proteins was acid labile and is mostly attributable to acetaldehyde. Additional evidence was attempted   through studies where the acetaldehyde was identified as its 2,4-dinitrophenylhydrazone or as its pentafluorphenylhydrazone   and gas chromatography (GC) analysis using electron capture detection. Values obtained were close to   detection limit and of variable nature. The covalent binding to nuclear lipids involved phospholipids, fatty acids and   esters and cholesterol free and esterified and it was only partially labile to acid treatment. Production of ethanol   reactive metabolites such as acetaldehyde and free radicals, nearby liver nuclear DNA and nuclear proteins or lipids,   might have significant toxicological consequences. © 1999 Elsevier Science Ireland Ltd.