TY - JOUR
T1 - Increased oxidation of ethylene glycol to formaldehyde by microsomes after ethanol treatment
T2 - role of oxygen radicals and cytochrome P450
AU - Kukielka, Ewa
AU - Cederbaum, Arthur I.
N1 - Funding Information:
* These studies were supported by USPHS Grant AA-03312 and AA-03508 (Alcohol Research Center) from The National Institute on Alcohol Abuse and Alcoholism. We thank Dr. Liviu Clejan for providing the anti-P4502E1 IgG and Ms. War Visco Cenizal for typing the manuscript. * Corresponding author, Tel.: 212 241 7285; Fax: 212 996 7214.
PY - 1995/6
Y1 - 1995/6
N2 - 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{A figure is presented} 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.
AB - 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{A figure is presented} 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.
KW - Chronic ethanol
KW - Ethylene glycol
KW - Formaldehyde
KW - Microsomal production
UR - http://www.scopus.com/inward/record.url?scp=0029060029&partnerID=8YFLogxK
U2 - 10.1016/0378-4274(94)03225-V
DO - 10.1016/0378-4274(94)03225-V
M3 - Article
C2 - 7604403
AN - SCOPUS:0029060029
SN - 0378-4274
VL - 78
SP - 9
EP - 15
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1
ER -