Beaune P, Bourdi M, Belloc C, Gautier J C, Guengerich F P, Valadon P
Inserm U75, CHU Necker, Laboratoire de Biochimie, Paris, France.
Toxicology. 1993 Oct 5;82(1-3):53-60. doi: 10.1016/0300-483x(93)90059-2.
Drug-induced hepatitis can be caused by an abnormal immunological response. In the case of tienilic acid- and dihydralazine-induced hepatitis, we postulated a scheme in which a P450 produced a reactive metabolite (step 1); this reactive metabolite bound to the P450 producing it (step 2) leading to a neoantigen triggering the immune response (step 3); the autoantibodies produced during the immune response recognized the P450 producing the reactive metabolite (step 4). The use of microorganisms (yeast or bacteria) expressing cloned human P450 helped in proving some steps of this postulated scheme, particularly steps 1 and 4.
药物性肝炎可由异常免疫反应引起。以替尼酸和肼屈嗪所致肝炎为例，我们提出了一个机制：一种细胞色素P450产生一种反应性代谢产物（步骤1）；这种反应性代谢产物与产生它的细胞色素P450结合（步骤2），导致一种新抗原触发免疫反应（步骤3）；免疫反应过程中产生的自身抗体识别产生反应性代谢产物的细胞色素P450（步骤4）。利用表达克隆化人细胞色素P450的微生物（酵母或细菌）有助于证实该推测机制的某些步骤，尤其是步骤1和步骤4。
