Andronik-Lion V, Boucher J L, Delaforge M, Henry Y, Mansuy D
Laboratorie de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA400, Université René Descartes, France.
Biochem Biophys Res Commun. 1992 May 29;185(1):452-8. doi: 10.1016/s0006-291x(05)81006-x.
Rat liver microsomes catalyze the oxidation of para-hexyloxy-benzamidoxime 1 to the corresponding arylamide 2 and NO2-, by NADPH and O2. Involvement of cytochromes P450 as catalysts of this reaction was shown by the strong inhibitory effects of CO and miconazole and the spectacular increase of the activity upon treatment of rats with dexamethasone, a specific inducer of cytochromes P450 of the 3A subfamily. Formation of NO during oxidation of 1 was shown by detection of the formation of cytochrome P450- and cytochrome P420-Fe(II)-NO complexes by visible and EPR spectroscopy. The formation of these complexes should be responsible, at least in part, for the fast decrease of the rate of microsomal oxidation of 1 with time. These results suggest that exogenous compounds containing amidine or amidoxime functions could act as precursors of NO in vivo after in situ oxidation by cytochromes P450.
大鼠肝脏微粒体可通过NADPH和O₂将对己氧基苯甲脒肟1催化氧化为相应的芳基酰胺2和NO₂⁻。CO和咪康唑具有强烈的抑制作用，而用3A亚家族细胞色素P450的特异性诱导剂地塞米松处理大鼠后，该反应的活性显著增加，这表明细胞色素P450参与了此反应的催化过程。通过可见光谱和电子顺磁共振光谱检测到细胞色素P450-和细胞色素P420-Fe(II)-NO复合物的形成，表明在1氧化过程中会形成NO。这些复合物的形成至少部分地导致了微粒体对1的氧化速率随时间快速下降。这些结果表明，含有脒或脒肟官能团的外源化合物在被细胞色素P450原位氧化后，可能在体内充当NO的前体。
