人足月胎盘微粒体中NADPH依赖的药物氧化还原循环与脂质过氧化作用

NADPH-dependent drug redox cycling and lipid peroxidation in microsomes from human term placenta.

Byczkowski J Z, Kulkarni A P

Florida Toxicology Research Center, College of Public Health, University of South Florida, Tampa 33612.

Int J Biochem. 1989;21(2):183-90. doi: 10.1016/0020-711x(89)90107-9.

Abstract

NADPH-dependent iron and drug redox cycling, as well as lipid peroxidation process were investigated in microsomes isolated from human term placenta. 2. Paraquat and menadione were found to undergo redox cycling, catalyzed by NADPH:cytochrome P-450 reductase in placental microsomes. 3. The drug redox cycling was able to initiate microsomal lipid peroxidation in the presence of micromolar concentrations of iron and ethylenediaminetetraacetate (EDTA). 4. Superoxide was essential for the microsomal lipid peroxidation in the presence of iron and EDTA. 5. Drastic peroxidative conditions involving superoxide and prolonged incubation in the presence of iron were found to destroy flavin nucleotides, inhibit NADPH:cytochrome P-450 reductase and inhibit propagation step of lipid peroxidation. 6. Reactive oxo-complex formed between iron and superoxide is proposed as an ultimate species for the initiation of lipid peroxidation in microsomes from human term placenta as well as for the destruction of flavin nucleotides and inhibition of NADPH:cytochrome P-450 reductase as well as for impairment of promotion of lipid peroxidation under drastic peroxidative conditions.

摘要

对从足月人胎盘分离出的微粒体中的NADPH依赖性铁和药物氧化还原循环以及脂质过氧化过程进行了研究。2. 发现百草枯和甲萘醌在胎盘微粒体中由NADPH：细胞色素P-450还原酶催化进行氧化还原循环。3. 在存在微摩尔浓度的铁和乙二胺四乙酸（EDTA）的情况下，药物氧化还原循环能够引发微粒体脂质过氧化。4. 超氧化物对于在存在铁和EDTA的情况下的微粒体脂质过氧化至关重要。5. 发现涉及超氧化物的剧烈过氧化条件以及在存在铁的情况下长时间孵育会破坏黄素核苷酸，抑制NADPH：细胞色素P-450还原酶并抑制脂质过氧化的传播步骤。6. 铁和超氧化物之间形成的反应性氧络合物被认为是足月人胎盘微粒体中脂质过氧化起始的最终物质，也是黄素核苷酸破坏、NADPH：细胞色素P-450还原酶抑制以及在剧烈过氧化条件下脂质过氧化促进受损的原因。