化学诱导的肾毒性：代谢活化的作用。

Chemically induced nephrotoxicity: role of metabolic activation.

作者信息

Rush G F, Smith J H, Newton J F, Hook J B

出版信息

Crit Rev Toxicol. 1984;13(2):99-160. doi: 10.3109/10408448409034079.

Abstract

Renal xenobiotic metabolism can result in production of electrophiles or free radicals that may covalently bind macromolecules or initiate lipid peroxidation. The mechanisms of renal xenobiotic metabolism may vary in different anatomical regions. Kidney cortex contains a cytochrome P-450 system while medulla contains a prostaglandin endoperoxidase. Recently cysteine conjugated-lyase has been implicated in production of reactive intermediates. Metabolic activation may be amplified by accumulation of xenobiotics within renal cells due to tubular concentrating and/or secretory mechanisms. Additionally, renal xenobiotic detoxicification can occur by conjugation with glucuronide, sulfate or glutathione.

摘要

肾脏对外源生物活性物质的代谢可导致亲电试剂或自由基的产生，这些物质可能会与大分子共价结合或引发脂质过氧化。肾脏对外源生物活性物质的代谢机制在不同的解剖区域可能有所不同。肾皮质含有细胞色素P - 450系统，而髓质含有前列腺素内过氧化物酶。最近，半胱氨酸共轭裂解酶被认为与活性中间体的产生有关。由于肾小管的浓缩和/或分泌机制，外源生物活性物质在肾细胞内的积累可能会放大代谢活化作用。此外，肾脏对外源生物活性物质的解毒作用可通过与葡萄糖醛酸、硫酸盐或谷胱甘肽结合来实现。