乙醇对离体大鼠肝细胞乙基吗啡代谢的影响:用多室模型表征。
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许宝强，Aasmundstad TA, Lillekjendlie B, Bjorneboe A, Christophersen AS, Morland J
乙醇对离体大鼠肝细胞乙基吗啡代谢的影响:用多室模型表征。
中华毒物学杂志，1997,30(4):391 - 391。
- PubMed ID
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9140136 (PubMed视图］
- 摘要
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肝细胞色素P-450酶介导可待因和乙基吗啡至少两个重要的生物转化途径，从n -去甲基化或o -脱烷基化开始，产生极性代谢物，随后葡萄糖醛酸化。本研究旨在描述乙醇对乙基吗啡代谢的急性影响，并将其与新鲜分离的大鼠肝细胞悬液中对可待因的影响进行比较。采用胶原酶灌注法制备雄性Wistar大鼠肝细胞。采用高效液相色谱-紫外检测法测定乙基吗啡、可待因及其代谢产物的含量。乙醇浓度为5mM时，乙基吗啡总消除率降低12%;乙醇浓度为100 mM时，乙基吗啡总消除率降低38%。可待因的相应百分比分别为16%和43%。在乙醇存在的情况下，乙基吗啡和可待因的几种中间产物和终产物的浓度与对照情况相比有明显变化。将实验数据应用于数学区室线性模型，以估计乙醇对两种主要代谢途径中分离反应速率的影响。乙基吗啡实验在100和0 mM乙醇条件下的反应速率常数之比分别为:乙基吗啡->去甲吗啡0.65，去甲吗啡->去甲吗啡0.63，乙基吗啡->吗啡0.56，吗啡->去甲吗啡0.49，去甲吗啡->去甲吗啡-3-葡糖苷0.31，吗啡->吗啡-3-葡糖苷0.49。乙醇对可待因代谢的影响几乎类似。 In additional experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine was found to be inhibited by ethanol in a concentration-dependent manner. The glucuronidation of morphine and normorphine added in separate experiments was also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to 60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100 mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine-3-glucuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.
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