Kukiełka E, Cederbaum A I
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Toxicol Lett. 1995 Jun;78(1):9-15. doi: 10.1016/0378-4274(94)03225-v.
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.
通过检测乙二醇生成甲醛的情况，测定了乙醇喂养大鼠和配对喂养对照大鼠微粒体产生高铁血红素型氧化剂的能力。乙醇喂养大鼠的微粒体在氧化乙二醇方面比对照大鼠的微粒体更具活性。过氧化氢酶是该反应的强效抑制剂，超氧化物歧化酶有轻微抑制作用，而羟基自由基清除剂则无作用。这些结果表明，在将乙二醇氧化为甲醛的整个途径中，过氧化氢（H₂O₂）起着重要作用，而超氧阴离子（O₂⁻）或羟基自由基（·OH）则不然。乙醇处理后，微粒体产生过氧化氢的量增加，增加程度与乙二醇氧化的增加程度相对应。多种细胞色素P450抑制剂和配体，包括咪康唑、二乙基二硫代氨基甲酸盐、色胺和4-甲基吡唑，均抑制了两种微粒体制剂产生甲醛的能力。抗细胞色素P4502E1免疫球蛋白也抑制了两种微粒体制剂的反应，并阻止了乙醇处理引起的增加。这些结果表明，乙醇处理大鼠的微粒体在产生高铁血红素型氧化剂方面比配对喂养对照大鼠的微粒体更具活性，并且细胞色素P4502E1产生过氧化氢的增加在乙二醇氧化为甲醛的增加中起作用。
