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百草枯肝微粒体生物转化过程中羟自由基形成的证据,而硝呋替莫则没有。一项二甲基亚砜清除研究。

Evidence for hydroxyl free radical formation during paraquat but not for nifurtimox liver microsomal biotransformation. A dimethyl-sulfoxide scavenging study.

作者信息

Castro G D, Lopez A, Castro J A

机构信息

Centro de Investigaciones Toxicológicas, CITEFA/CONICET, Buenos Aires, Argentina.

出版信息

Arch Toxicol. 1988;62(5):355-8. doi: 10.1007/BF00293623.

DOI:10.1007/BF00293623
PMID:3242445
Abstract

The effect of several experimental conditions on methane (CH4) production from dimethylsulfoxide (DMSO) in incubation mixtures containing liver microsomes and NADPH generating systems was studied. The process was heat sensitive in part but a significant fraction was non-enzymatic in nature. CH4 formation from DMSO was not significantly modified by 2-diethylaminoethyl-2,2-diphenylvalerate. HC 1 (SKF 525A) or EDTA 1 mM and significantly enhanced under an atmosphere of (CO 80% + O2 20%) rather than under air. A marked increase in CH4 production was observed when paraquat (PQ) was included in incubation mixtures but not when nifurtimox (Nfx) was added. Results support the hypothesis of hydroxyl free radical (.OH) formation during PQ biotransformation but cast doubts about its production for the case of Nfx. The low temperature gas chromatographic separation of d3-CH4 from CH4 described opens the future possibility for detecting trace formation of .OH in vivo, without interference from fecal CH4 formation by administering d6-DMSO to animals and collecting exhaled gases produced, in chambers containing the entire animal.

摘要

研究了几种实验条件对含有肝微粒体和NADPH生成系统的孵育混合物中二甲基亚砜(DMSO)产生甲烷(CH4)的影响。该过程部分对热敏感,但很大一部分本质上是非酶促的。2-二乙氨基乙基-2,2-二苯基戊酸酯、HC 1(SKF 525A)或1 mM乙二胺四乙酸(EDTA)对DMSO生成CH4的过程没有显著影响,而在(80% CO + 20% O2)气氛下而非空气中,CH4生成显著增强。当在孵育混合物中加入百草枯(PQ)时,观察到CH4产量显著增加,但加入硝呋替莫(Nfx)时则没有。结果支持了PQ生物转化过程中形成羟基自由基(·OH)的假说,但对Nfx情况下羟基自由基的产生存在疑问。所描述的从CH4中低温气相色谱分离d3-CH4,为通过给动物施用d6-DMSO并在包含整个动物的舱室中收集产生的呼出气体,在不受到粪便CH4形成干扰的情况下检测体内·OH的微量形成开辟了未来可能性。

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1
Evidence for hydroxyl free radical formation during paraquat but not for nifurtimox liver microsomal biotransformation. A dimethyl-sulfoxide scavenging study.百草枯肝微粒体生物转化过程中羟自由基形成的证据,而硝呋替莫则没有。一项二甲基亚砜清除研究。
Arch Toxicol. 1988;62(5):355-8. doi: 10.1007/BF00293623.
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NADH-dependent microsomal interaction with ferric complexes and production of reactive oxygen intermediates.烟酰胺腺嘌呤二核苷酸(NADH)依赖的微粒体与铁复合物的相互作用及活性氧中间体的产生。
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[Inhibition of lipid peroxidation in liver microsomes by nifurtimox and nitrofurantoin].[硝呋替莫和呋喃妥因对肝微粒体脂质过氧化的抑制作用]
Medicina (B Aires). 1987;47(4):342-50.

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本文引用的文献

1
Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment.硝呋替莫治疗后大鼠肝脏胆汁分泌增加及肝内谷胱甘肽丢失。
Biochem Pharmacol. 1983 Feb 1;32(3):483-7. doi: 10.1016/0006-2952(83)90527-0.
2
Paraquat-induced chemiluminescence of microsomal fractions.百草枯诱导的微粒体组分化学发光
Biochem Pharmacol. 1983 Jan 1;32(1):147-50. doi: 10.1016/0006-2952(83)90667-6.
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Effect of dimethylthiourea on paraquat toxicity in rats.二甲基硫脲对大鼠百草枯毒性的影响。
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Paraquat: model for oxidant-initiated toxicity.百草枯:氧化应激引发毒性的模型。
Environ Health Perspect. 1984 Apr;55:37-46. doi: 10.1289/ehp.845537.
5
Production of formaldehyde during metabolism of dimethyl sulfoxide by hydroxyl radical generating systems.由羟基自由基生成系统在二甲基亚砜代谢过程中产生甲醛。
Biochemistry. 1981 Oct 13;20(21):6006-12. doi: 10.1021/bi00524a013.
6
Generation of free radicals induced by nifurtimox in mammalian tissues.硝呋替莫在哺乳动物组织中诱导产生自由基。
J Biol Chem. 1981 Nov 10;256(21):10930-3.
7
Nitrofuran enhancement of microsomal electron transport, superoxide anion production and lipid peroxidation.呋喃妥因对微粒体电子传递、超氧阴离子生成及脂质过氧化的增强作用。
Arch Biochem Biophys. 1981 Apr 1;207(2):316-24. doi: 10.1016/0003-9861(81)90039-4.
8
Species and sex differences in the kinetic constants for the N-demethylation of ethyl-morphine by liver microsomes.肝脏微粒体对乙基吗啡进行N-去甲基化反应的动力学常数的种属和性别差异。
Biochem Biophys Res Commun. 1967 Aug 7;28(3):426-30. doi: 10.1016/0006-291x(67)90329-4.
9
Studies on pentane evolution by rats treated with nifurtimox or benznidazole.用硝呋替莫或苯硝唑治疗的大鼠戊烷释放情况的研究。
Toxicology. 1985 Jun 28;35(4):319-26. doi: 10.1016/0300-483x(85)90065-4.
10
Benznidazole and nifurtimox nitroreductase activity in liver microsomes from male rats preinduced with phenobarbital or 3-methylcholanthrene.苯巴比妥或3-甲基胆蒽预诱导的雄性大鼠肝微粒体中苯并硝唑和硝呋替莫的硝基还原酶活性。
Res Commun Chem Pathol Pharmacol. 1985 Dec;50(3):443-6.