饮食的影响鞣花酸在大鼠肝和食管粘膜细胞色素P450和二期的酶。

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安D, D推杆,Kresty L,碎石机GD,弗洛姆D, Hollenberg PF

饮食的影响鞣花酸在大鼠肝和食管粘膜细胞色素P450和二期的酶。

致癌作用。1996年4月17日(4):821 - 8。

PubMed ID

8625497 (在PubMed

]

文摘

鞣花酸(EA),一种天然植物多酚具有广泛chemoprotective属性。饮食EA已经被证明可以减少发病率N-2-fluorenylacetamide-induced hepatocarcinogenesis在老鼠和N-nitrosomethylbenzylamine (NMBA)全身的大鼠食管肿瘤。在这项研究中表达的变化和活动特定的鼠肝和食管粘膜细胞色素P450酶(P450)和二期后饮食EA治疗了。肝脏和食管粘膜微粒体和胞质是由三组费舍尔344老鼠喂养一个ain - 76饮食不含或0.4或4.0克/公斤EA 23天。在肝脏总P450含量下降了25%,P450 2 e1-catalyzed p-nitrophenol羟基化下降了15%。没有观察到变化P450 1 a1, 2 b1或3 a1/2表达式或活动或细胞色素b5活动。P450还原酶活性下降了28%。微粒体环氧化物水解酶(咩)表达式EA治疗后下降了85%,但咩活动并没有改变。谷胱甘肽S-transferase肝二期酶(GST), NAD (P) H:醌还原酶(NAD (P) H: QR)和UDP glucuronosyltransferase (UDPGT)活动增加了26个,分别为17岁和75%。化验为特定形式的销售税表示显著增加的活动同功酶2(190%),4 - 4(150%)和盘中(82%)。 In the rat esophageal mucosa only P450 1A1 could be detected by Western blot analysis and androstendione was the only P450 metabolite of testosterone detectable. However, there were no differences in the expression of P450 1A1, the formation of androstendione or NAD(P)H:QR activities between control and EA-fed rats in the esophagus. Although there was no significant decrease in overall GST activity, as measured with 1-chloro-2,4-dinitrobenzene (CDNB), there was a significant decrease in the activity of the 2-2 isozyme (66% of control). In vitro incubations showed that EA at a concentration of 100 microM inhibited P450 2E1, 1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2 activity. Using standard steady-state kinetic analyses, EA was shown to be a potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, with apparent Ki values of approximately 55 and 14 microM respectively. In conclusion, these results demonstrate that EA causes a decrease in total hepatic P450 with a significant effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities [GST, NAD-(P)H:QR and UDPGT] and decreases hepatic mEH expression. It also inhibits the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective effect of EA against various chemically induced cancers may involve decreases in the rates of metabolism of these carcinogens by phase I enzymes, due to both direct inhibition of catalytic activity and modulation of gene expression, in addition to effects on the expression of phase II enzymes, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates.

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药物酶

药物	酶	类	生物	药理作用	行动
鞣花酸	细胞色素P450 2 e1	蛋白质	人类	未知的	抑制剂	细节