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使用亲脂性中空纤维膜的酶促解毒:III. 硫化物的氧化反应。

Enzymatic detoxification using lipophilic hollow-fiber membranes: III. Oxidation reactions of sulfides.

作者信息

Yamamoto Y, Tsikas D, Brunner G

机构信息

Division of Gastroenterology and Hepatology, Medizinische Hochschule, Hannover, F.R.G.

出版信息

Artif Organs. 1989 Apr;13(2):103-8. doi: 10.1111/j.1525-1594.1989.tb02844.x.

DOI:10.1111/j.1525-1594.1989.tb02844.x
PMID:2705882
Abstract

A lipophilic hollow-fiber membrane preparation that was previously described for glucuronidation and sulfation reactions was used for the enzymatic oxidation of sulfides. Endogenous and exogenous toxins in buffer solution or in serum or blood of intoxicated animals were circulated through the internal lumen of lipophilic hollow fibers. Native liver microsomes of the rabbit were circulated on the outside of the hollow fibers. Lipophilic toxins accumulate in and penetrate through the lipophilic membrane and the toxins are oxidized by the mixed function oxygenase system of liver microsomes. The oxidized products cannot rediffuse to the donor side. The endogenous toxin dimethylsulfide (DMS) was converted on the enzyme side to dimethylsulfoxide (DMSO) and small amounts of dimethylsulfone, which are hydrophilic and nontoxic substances. Other sulfide compounds, ethylmethylsulfide (EMS) and s-butylmethylsulfide (BMS), have also been converted to their oxidized forms. The enzymatic clearance of the hollow-fiber module for DMS in in vivo experiments in the rabbit was found to be 1.30 nmol/h/mg protein/cm2 hollow-fiber surface. The transmembranous enzymatic clearance of the in vitro oxidation reactions of DMS, EMS, and BMS in buffer solutions (open circuit) were measured, respectively, as 1.63, 3.45, and 5.16 nmol/h/mg protein/cm2 hollow-fiber surface. This technique allows the enzymatic oxidation of sulfur compounds with liver microsomes in vitro and in vivo without immunological hazards, and it is suited for artificial liver support.

摘要

一种先前用于葡萄糖醛酸化和硫酸化反应的亲脂性中空纤维膜制剂被用于硫化物的酶促氧化。缓冲溶液中或中毒动物血清或血液中的内源性和外源性毒素通过亲脂性中空纤维的内腔循环。兔的天然肝微粒体在中空纤维外部循环。亲脂性毒素积聚并穿透亲脂性膜,这些毒素被肝微粒体的混合功能氧化酶系统氧化。氧化产物不能再扩散到供体侧。内源性毒素二甲基硫醚(DMS)在酶侧转化为二甲基亚砜(DMSO)和少量二甲基砜,它们是亲水性且无毒的物质。其他硫化物化合物,如乙甲基硫醚(EMS)和仲丁基甲基硫醚(BMS),也已转化为其氧化形式。在兔体内实验中,发现中空纤维模块对DMS的酶促清除率为1.30 nmol/h/mg蛋白质/cm²中空纤维表面。分别测定了缓冲溶液(开路)中DMS、EMS和BMS体外氧化反应的跨膜酶促清除率,分别为1.63、3.45和5.16 nmol/h/mg蛋白质/cm²中空纤维表面。该技术允许在体外和体内用肝微粒体对硫化合物进行酶促氧化,而无免疫危害,适用于人工肝支持。

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