Abstract：
Fungal anthraquinones dermocybin and dermorubin are attractive alternatives for synthetic dyes but their metabolism is largely unknown. We conducted a qualitative in vitro study to identify their metabolism using human liver microsomes and cytosol, as well as recombinant human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes. Additionally, liver microsomal and cytosolic fractions from rat, mouse and pig were used. Following incubations of the biocolourants with the enzymes in the presence of nicotinamide adenine dinucleotide phosphate, UDP-glucuronic acid, 3\'-phosphoadenosine-5\'-phosphosulfate (PAPS) or S-adenosyl methionine (SAM) to enable CYP oxidation, glucuronidation, sulfonation or methylation, we observed several oxidation and conjugation metabolites for dermocybin but none for dermorubin. Human CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A7 catalysed dermocybin oxidation. The formation of dermocybin glucuronides was catalysed by human UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10 and 2B15. Human SULT1B1, 1C2 and 2A1 sulfonated dermocybin. Dermocybin oxidation was faster than conjugation in human liver microsomes. Species differences were seen in dermocybin glucuronidation between human, rat, mouse and pig. In conclusion, many CYP and conjugation enzymes metabolized dermocybin, whereas dermorubin was not metabolized in human liver fractions in vitro. The results indicate that dermocybin would be metabolized in humans in vivo.
摘要：
真菌蒽醌类皮胞苷和皮胆红素是合成染料的有吸引力的替代品，但它们的代谢在很大程度上是未知的。我们进行了定性的体外研究，以确定他们的代谢使用人肝微粒体和细胞质，以及重组人细胞色素P450（CYP），UDP-葡糖醛酸基转移酶(UGT)和磺基转移酶(SULT)酶。此外,来自大鼠的肝微粒体和胞质部分，使用小鼠和猪。在存在烟酰胺腺嘌呤二核苷酸磷酸的情况下，将生物色素与酶一起孵育后，UDP-葡萄糖醛酸，3'-磷酸腺苷-5'-磷酸硫酸盐（PAPS）或S-腺苷甲硫氨酸（SAM）使CYP氧化，葡糖醛酸化，磺化或甲基化，我们观察到皮肤细胞素的几种氧化和结合代谢物，但没有观察到皮肤胆红素。人CYP1A1、1A2、1B1、2A6、2B6、2C8、2C9、2C19、2D6、2E1、3A4和3A7催化皮胞嘧啶氧化。人UGT1A1、1A3、1A7、1A8、1A9、1A10和2B15催化了皮胞嘧啶葡糖苷酸的形成。人SULT1B1、1C2和2A1磺化皮细胞素。在人肝微粒体中，皮蛋白聚糖的氧化比结合更快。在人类之间的皮蛋白聚糖葡糖醛酸化中观察到物种差异，rat,老鼠和猪总之,许多CYP和缀合酶代谢皮肤细胞素，而在体外的人肝脏部分中，皮胆红素没有代谢。结果表明，人体内会代谢皮肤细胞素。
