Increased oxidation of ethylene glycol to formaldehyde by microsomes after ethanol treatment: role of oxygen radicals and cytochrome P450.
The production of ferryl-type oxidants by microsomes from ethanol-fed rats and pair-fed controls was determined by assaying for the production of formaldehyde from ethylene glycol. Microsomes from the ethanol-fed rats were more reactive than controls in oxidizing ethylene glycol. Catalase was a powerful inhibitor for this reaction, superoxide dismutase was slightly inhibitory and hydroxyl radical scavengers had no effect. These results suggest an important role for H2O2, but not O2-. or .OH in the overall pathway for oxidizing ethylene glycol to formaldehyde. The production of H2O2 by microsomes was increased after ethanol treatment, the extent of increase corresponding to the increase in oxidation of ethylene glycol. A variety of inhibitors and ligands of cytochrome P450, including miconazole, diethyldithiocarbamate, tryptamine, and 4-methylpyrazole, inhibited formaldehyde production by both microsomal preparations. Anti-cytochrome P4502E1 IgG also inhibited the reaction with both microsomal preparations and prevented the increase caused by ethanol treatment. These results indicate that microsomes from ethanol-treated rats are more reactive than pair-fed controls in generating ferryl-type oxidants and that increased production of H2O2 by cytochrome P4502E1 plays a role in the elevated oxidation of ethylene glycol to formaldehyde.
Kukiełka
E
E
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Cederbaum
A I
AI
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000378:metabolism*; D005557:Formaldehyde / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013997:Time Factors
D065607:Cytochrome P-450 Enzyme Inhibitors; D005026:Ethylene Glycols; D005609:Free Radicals; D017382:Reactive Oxygen Species; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System; D019855:Ethylene Glycol