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題 名 | Metabolic Characteristics and Enflurane Defluorination of Cytochrome P450-Dependent Monooxygenases in Human Hepatocellular Carcinoma=人類肝細胞癌細胞色素P450單氧酵素系統代謝特性及Enflurane去氟化之研究 |
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作 者 | 陳大樑; 侯文詠; 孫維仁; 吳鋼治; 王國清; 彭文玲; 林珍榮; | 書刊名 | 麻醉學雜誌 |
卷 期 | 35:1 1997.03[民86.03] |
頁 次 | 頁7-14 |
分類號 | 416.5 |
關鍵詞 | 藥物代謝; 去氟化活性; 肝細胞癌; 酵素; 細胞色素P450單氧酵素; Metabolism:defluorination; Carcinoma:hepatocellular; Enzymes:cytochrome P450 monooxygenases; |
語 文 | 英文(English) |
中文摘要 | 背景:原發性肝細胞癌好發於東方人尤其是中國人之中,該類病人經診斷後,多 半會接受手術、 化學藥物等治療, 而暴露於各種藥物之下, 因此瞭解這類病人細胞色素 P450 酵素系統,代謝外來物質及吸入性麻醉劑的能力,具有臨床的意義, 亦為本研究探討 的主題。 方法:八位原發性肝細胞癌病人,經外科手術切除後之新鮮肝癌及正常部份肝組織,與五位 非肝臟疾病病人之肝組織做比較, 評估組織中細胞 P450 含量,以及同型酵素 P450 1A1, 2B1 及 2E1 之代謝活性,並以 Enflurane 去氟化活性,來評估其對於吸入性麻醉劑代謝之 能力。 結果:肝細胞癌組織微粒體蛋白含量明顯下降,細胞色素 P450 總量及各組成酵素均減少( p<0.01 ),癌細胞遠端之正常肝組織酵素含量,雖比對照正常組稍低, 但統計上並無差別 。酵素活性方面,細胞色素 P450 1A1, 2B1 及 2E1 活性均下降,以特殊受質代謝反應下降 程度而言,依序為 1A1 ≧ 2B1 ≧ 2E1。 至於對 Enflurane 去氟化之活性,肝癌組織亦大 幅降低( p<0.05 )。 結論:肝細胞癌病人肝內細胞色素 P450 酵素含量及活性均減少,意謂此類病人對於藥物之 活化與去活化能力均下降,因此在接受各種藥物治療時,應考慮其藥物動力學之改變,以及 可能影響之藥物交互作用。 |
英文摘要 | Background: Xenobiotic metabolism and defluorination capacity of microsomal monooxygenases were in-vestigated in vitro through the surgical sp ecimens of liver resected from patients with hepatocellular carcinoma and patients of extrahepatic pathology as control. Methods: In microsomes of hepatocellular carcinoma tissues, the activities of cytochrome P450-dependent monooxygenase isozymes 1A1, 2B1, and 2E1 were evaluated in vitro by reacting with the specific marker substrates benzo(a) pyrene, benzphetamine and anililne, respectively, in the generating incubation system. The distant normal liver tissues and tissues from control patients with extrahepatic lesion extrahepatic lesion were also investigated for comparison. The ability of enflurane defluorination was assessed by Orion combined electrode for detection of free fluoride ion production. Results: Concentrations of P450 total content, cytochrome b ��, and NADPH-cytochrome c reductase showed parallel and marked reduction in tumor tissues when compared with its distant normal regions or normal livers. The monooxygenase functions displayed significant decreases within the tumor tissues as benzo(a) pyrene hydroxylation ≧�� benzphetamine demethylation > aniline hydroxylation inmagnitude, Defluorination of enflurane also markedly decreased in tumor tissues comparing with normal livers. Conclusions: These marked reductions in the compositions and in vitro metablic activities, including defluorination of anesthetics, in the cytochrome P450-dependent monooxygenases within the tumor tissues characterize the unique pattern of xenobiotic metabolism in patients with hepatocellular carcinoma. �� |
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