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Isothiocyanates and Xenobiotic Detoxification
Molecular Nutrition & Food Research ( IF 5.2 ) Pub Date : 2018-02-12 , DOI: 10.1002/mnfr.201700916
Ahmad Faizal Abdull Razis 1 , Nattaya Konsue 2, 3 , Costas Ioannides 3
Affiliation  

The potential of isothiocyanates to antagonize the carcinogenicity of structurally diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision‐cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism‐based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S‐transferase, epoxide hydrolase, and UDP‐glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increases the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to upregulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated.

中文翻译:

异硫氰酸盐和异物解毒

在动物中已经建立了异硫氰酸酯拮抗结构多样的化学物质致癌性的潜力。一种可行的作用机制包括通过抑制化学致癌物的生成和/或刺激其解毒作用来降低其化学毒性的遗传毒性代谢物的可用性来保护DNA。在大鼠/人原代肝细胞和精确切割的组织切片中进行的体内和体外研究表明,异硫氰酸盐会损害细胞色素P450的活性,包括CYP1家族,该家族在致癌物的生物激活中最活跃,原因是基于机制的灭活剂。芳族异硫氰酸苯乙酯是最有效的研究方法,而脂肪族异硫氰酸盐(例如萝卜硫烷和芥酸)则需要高剂量才能表现出这种饮食效果,而这种饮食效果可能并非总能通过饮食获得。在所有研究的系统中,异硫氰酸盐都是排毒酶系统的强力诱导剂,包括醌还原酶,谷胱甘肽S-转移酶,环氧水解酶和UDP-葡萄糖醛酸转移酶。实际上,在吸烟者中,异硫氰酸苯乙酯的摄入增加了烟草中存在的有毒化学物质的非活性巯基代谢产物的尿排泄。异硫氰酸酯的前体芥子油苷也具有上调解毒酶系统的潜力,但它们对与十字花科蔬菜食用有关的化学预防癌症的贡献尚待评估。
更新日期:2018-02-12
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