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代谢活化在化学诱导的肺部疾病发病机制中的作用：肺毒性呋喃4-异戊烯醇的作用机制

Role of metabolic activation in the pathogenesis of chemically induced pulmonary disease: mechanism of action of the lung-toxic furan, 4-ipomeanol.

作者信息

Boyd M R

出版信息

Environ Health Perspect. 1976 Aug;16:127-38. doi: 10.1289/ehp.7616127.

DOI:10.1289/ehp.7616127
PMID:1017416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1475220/
Abstract

Many xenobiotics produce hepatic injury due to their metabolism in the liver to highly reactive electrophile intermediates which form covalent conjugates with nucleophilic cellular constituents. This presentation describes studies indicating that the production of chemically reactive metabolites by pulmonary metabolism of xenobiotics can also play a fundamental role in the pathogenesis of chemically induced lung disease.

摘要

许多外源性物质在肝脏中代谢生成高反应性亲电中间体，这些中间体与亲核性细胞成分形成共价结合物，从而导致肝损伤。本报告描述的研究表明，外源性物质经肺代谢产生化学反应性代谢物在化学诱导性肺病的发病机制中也可发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/c6f58e103b93/envhper00491-0131-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/3a116e3e1239/envhper00491-0129-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/fca8c90e9853/envhper00491-0129-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/054b64534b19/envhper00491-0130-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/c6f58e103b93/envhper00491-0131-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/3a116e3e1239/envhper00491-0129-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/fca8c90e9853/envhper00491-0129-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/054b64534b19/envhper00491-0130-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592e/1475220/c6f58e103b93/envhper00491-0131-a.jpg

相似文献

1
Role of metabolic activation in the pathogenesis of chemically induced pulmonary disease: mechanism of action of the lung-toxic furan, 4-ipomeanol.代谢活化在化学诱导的肺部疾病发病机制中的作用：肺毒性呋喃4-异戊烯醇的作用机制
Environ Health Perspect. 1976 Aug;16:127-38. doi: 10.1289/ehp.7616127.
2
In vivo studies on the relationship between target organ alkylation and the pulmonary toxicity of a chemically reactive metabolite of 4-ipomeanol.关于靶器官烷基化与4-异戊烯醇化学反应性代谢物肺毒性之间关系的体内研究。
J Pharmacol Exp Ther. 1978 Dec;207(3):687-97.
3
Species and strain differences in target organ alkylation and toxicity by 4-ipomeanol. Predictive value of covalent binding in studies of target organ toxicities by reactive metabolites.
Biochem Pharmacol. 1979 Dec 1;28(23):3367-72. doi: 10.1016/0006-2952(79)90074-1.
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Effects of anti-NADPH-cytochrome c reductase and anti-cytochrome b5 antibodies on the hepatic and pulmonary microsomal metabolism and covalent binding of the pulmonary toxin 4-ipomeanol.抗NADPH-细胞色素c还原酶抗体和抗细胞色素b5抗体对肺毒素4-异戊烯醇的肝脏和肺微粒体代谢及共价结合的影响。
Biochem Biophys Res Commun. 1978 Sep 29;84(2):389-95. doi: 10.1016/0006-291x(78)90182-1.
5
In vitro studies on the metabolic activation of the pulmonary toxin, 4-ipomeanol, by rat lung and liver microsomes.大鼠肺和肝微粒体对肺毒素4-异戊二烯醇代谢激活的体外研究。
J Pharmacol Exp Ther. 1978 Dec;207(3):677-86.
6
The in vitro formation of glutathione conjugates with the microsomally activated pulmonary bronchiolar aklylating agent and cytotoxin, 4-ipomeanol.谷胱甘肽与经微粒体激活的肺细支气管烷基化剂及细胞毒素4-异戊二烯醇在体外形成共轭物的过程。
J Pharmacol Exp Ther. 1980 Oct;215(1):97-103.
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The relationship between the catalytic activities of rabbit pulmonary cytochrome P-450 isozymes and the lung-specific toxicity of the furan derivative, 4-ipomeanol.兔肺细胞色素P-450同工酶的催化活性与呋喃衍生物4-异戊烯醇的肺特异性毒性之间的关系。
Mol Pharmacol. 1982 Nov;22(3):738-44.
8
Renal toxicity due to reactive metabolites formed in situ in the kidney: investigations with 4-ipomeanol in the mouse.肾脏中因原位形成的反应性代谢产物导致的肾毒性：用4-异戊烯醇在小鼠身上进行的研究。
J Pharmacol Exp Ther. 1981 Mar;216(3):640-6.
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Protective role of endogenous pulmonary glutathione and other sulfhydryl compounds against lung damage by alkylating agents. Investigations with 4-ipomeanol in the rat.内源性肺谷胱甘肽及其他巯基化合物对烷基化剂所致肺损伤的保护作用。用4-异亚丙基丙酮对大鼠进行的研究。
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10
Distribution and metabolism of the pulmonary alkylating agent and cytotoxin, 4-ipomeanol, in control and diethylmaleate-treated rats.
Biochem Pharmacol. 1982 Apr 15;31(8):1585-9. doi: 10.1016/0006-2952(82)90384-7.

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本文引用的文献

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Toxicity of mould-damaged sweet potatoes (Ipomoea batatas).霉菌污染的红薯（甘薯）的毒性
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Species Differences in Microsomal Oxidation and Glucuronidation of 4-Ipomeanol: Relationship to Target Organ Toxicity.4-异亚丙基甘油的微粒体氧化和葡萄糖醛酸化的种属差异：与靶器官毒性的关系。
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Characterization of an Additional Splice Acceptor Site Introduced into CYP4B1 in Hominoidae during Evolution.进化过程中在类人猿中引入CYP4B1的一个额外剪接受体位点的特征分析。
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Identification of amino acid determinants in CYP4B1 for optimal catalytic processing of 4-ipomeanol.鉴定CYP4B1中用于4-异薄荷醇最佳催化加工的氨基酸决定簇。
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Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.Cyp4b1 基因敲除小鼠的构建及其在 Ipomeanol 激活和毒性中的作用。
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Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in patients with advanced hepatocellular carcinoma.对晚期肝细胞癌患者进行的4-异戊烯醇（一种天然存在的烷基化呋喃）的II期研究。
Invest New Drugs. 2001;19(1):69-76. doi: 10.1023/a:1006408803734.
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Acute effects of 4-ipomeanol on experimental lung tumors with bronchiolar or alveolar cell features in Syrian hamsters or C3H/HeNCr mice.4-异亚丙基莽草酸对叙利亚仓鼠或C3H/HeNCr小鼠具有细支气管或肺泡细胞特征的实验性肺肿瘤的急性影响。
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Ultrastructural pulmonary changes induced by intravenously administered 3-methylindole in goats.静脉注射3-甲基吲哚对山羊肺部造成的超微结构变化
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Isolation and characterization of 4-ipomeanol, a lung-toxic furanoterpenoid produced by sweet potatoes (Ipomoea batatas).
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A lung oedema factor from mouldy sweet potatoes (Ipomoea batatas).
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K-region epoxides of polycyclic hydrocarbons: formation and further metabolism by rat-lung preparations.
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Metabolism of polycyclic hydrocarbons by rat-lung preparations.大鼠肺组织制剂对多环烃的代谢
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2,3-Dihydro-2,3-dihydroxy-aflatoxin B1: an acid hydrolysis product of an RNA-aflatoxin B1 adduct formed by hamster and rat liver microsomes in vitro.2,3-二氢-2,3-二羟基黄曲霉毒素B1：仓鼠和大鼠肝脏微粒体在体外形成的RNA-黄曲霉毒素B1加合物的酸水解产物。
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