Bickers D R, Pathak M A
Natl Cancer Inst Monogr. 1984 Dec;66:77-84.
Psoralens, tricyclic furocoumarins with potent photosensitizing properties in the skin, are now widely used in the treatment of several dermatologic diseases. In this study, the metabolism of 4,5',8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP) was studied in mouse liver. Orally administered TMP is transformed into several metabolites, the major one of which is 4,8-dimethyl-5'-carboxypsoralen (DMCP) in both humans and mice. Orally administered 8-MOP is metabolized into at least 5 fluorescent moieties, including 8-hydroxypsoralen, the 4'5'-dihydro-diol of 8-MOP, and furocoumaric acid. The effects of 3 psoralens, 8-MOP, TMP, and isopsoralen (angelicin) on hepatic microsomal drug-metabolizing enzymes and cytochrome P-450 were assessed in mice and rats. Administered orally to CD-1 mice daily for 6 days, 8-MOP caused twofold to threefold increases in hepatic aryl hydrocarbon hydroxylase (AHH), ethylmorphine N-demethylase, and cytochrome P-450. The absorbance maximum of the induced cytochrome was at 450 nm. Aniline hydroxylase activity was unchanged. Chronic administration of 8-MOP to Skh:hairless-1 mice caused significant enhancement of hepatic ethylmorphine N-demethylase and cytochrome P-450 but had no effect on AHH, whereas chronically administered TMP had no significant effect on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
补骨脂素是一类在皮肤中具有强大光敏特性的三环呋喃香豆素，目前广泛应用于多种皮肤病的治疗。在本研究中，对4,5',8-三甲基补骨脂素（TMP）和8-甲氧基补骨脂素（8-MOP）在小鼠肝脏中的代谢进行了研究。口服给予的TMP会转化为多种代谢产物，在人和小鼠中主要的代谢产物都是4,8-二甲基-5'-羧基补骨脂素（DMCP）。口服给予的8-MOP会代谢为至少5种荧光部分，包括8-羟基补骨脂素、8-MOP的4'5'-二氢二醇以及呋喃香豆酸。评估了3种补骨脂素，即8-MOP、TMP和异补骨脂素（白芷素）对小鼠和大鼠肝脏微粒体药物代谢酶及细胞色素P-450的影响。每天给CD-1小鼠口服8-MOP，持续6天，可使肝脏芳烃羟化酶（AHH）、N-脱甲基酶和细胞色素P-450增加2至3倍。诱导的细胞色素在450nm处吸光度最大。苯胺羟化酶活性未改变。对无毛-1小鼠长期给予8-MOP可显著增强肝脏N-脱甲基酶和细胞色素P-450，但对AHH无影响，而长期给予TMP对这些参数均无显著影响。（摘要截选至250字）
