Brogan W C, Miles P R, Colby H D
Biochim Biophys Acta. 1983 Jul 29;758(2):114-20. doi: 10.1016/0304-4165(83)90291-x.
Incubation of guinea pig adrenal microsomes with 10(-6) M ferrous (Fe2+) ion and adrenal cytosol initiated high levels of lipid peroxidation as measured by the production of malonaldehyde. Cytosol or Fe2+ alone had little effect on microsomal malonaldehyde formation. When microsomes were incubated in the presence of Fe2+ and cytosol, malonaldehyde levels continued to increase for at least 60 min. Accompanying the lipid peroxidation was a decline in adrenal microsomal monooxygenase activities. The rates of metabolism of xenobiotics (benzphetamine demethylase, benzo[a]pyrene hydroxylase) as well as steroids (21-hydroxylation) decreased as malonaldehyde levels increased. In addition, cytochrome P-450 levels, NADPH- and NADH-cytochrome c reductase activities, and substrate interactions with cytochrome(s) P-450 decreased as lipid peroxidation progressed. Inhibition of lipid peroxidation by increasing microsomal protein concentrations during the incubation period prevented the changes in microsomal metabolism. Malonaldehyde had no direct effects on adrenal microsomal enzyme activities. The results indicate that lipid peroxidation may have significant effects on adrenocortical function, diminishing the capacity for both xenobiotic and steroid metabolism.
用10(-6)M亚铁离子（Fe2+）和肾上腺细胞溶质温育豚鼠肾上腺微粒体，可引发高水平的脂质过氧化反应，这可通过丙二醛的生成来测定。单独的细胞溶质或Fe2+对微粒体丙二醛的形成影响很小。当微粒体在Fe2+和细胞溶质存在的情况下温育时，丙二醛水平至少持续增加60分钟。伴随脂质过氧化反应的是肾上腺微粒体单加氧酶活性的下降。随着丙二醛水平的增加，外源性物质（苄非他明脱甲基酶、苯并[a]芘羟化酶）以及类固醇（21-羟化）的代谢速率降低。此外，随着脂质过氧化反应的进行，细胞色素P-450水平、NADPH-和NADH-细胞色素c还原酶活性以及底物与细胞色素P-450的相互作用均降低。在温育期间通过增加微粒体蛋白浓度来抑制脂质过氧化反应，可防止微粒体代谢的变化。丙二醛对肾上腺微粒体酶活性没有直接影响。结果表明，脂质过氧化反应可能对肾上腺皮质功能有显著影响，降低外源性物质和类固醇的代谢能力。
