Formation and metabolism of 6-(1-acetol)-8-(1-acetol)-rutin in foods and in vivo, and their cytotoxicity.

Formation and metabolism of 6-(1-acetol)-8-(1-acetol)-rutin in foods and in vivo, and their cytotoxicity.
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DOI:
10.3389/fnut.2022.973048
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发表时间:
2022
影响因子:
5
通讯作者:
Zheng, Jie
Zheng, Jie
中科院分区:
农林科学2区
文献类型:
--
作者:
Chen, Min;Liu, Pengzhan;Zhou, Hua;Huang, Caihuan;Zhai, Weiye;Xiao, Yuantao;Ou, Juanying;He, Jun;El-Nezami, Hani;Zheng, Jie

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甲基乙二醛(Methylglyoxal,MGO)是一种高活性的糖基化终产物(advanced glycation end products,AGEs)前体物质,在体内可形成糖基化终产物(advanced glycation end products,AGEs),导致代谢综合征和慢性疾病。它也是热加工食品中各种致癌物的前体,包括丙烯酰胺和甲基咪唑。R3可通过形成各种加合物有效地包覆MGO。然而,衍生的加合物的代谢和安全性关注较少。在这项研究中,芦丁的二-MGO加合物,即6-(1-丙酮醇)-8-(1-丙酮醇)-芦丁的光学异构体,在食品和体内进行了鉴定。口服芦丁后(100 mg/kg BW)时,血浆中15 min达到最大值15.80 μg/L,30 min后急剧下降至定量水平以下,在肾脏和粪便中仅检出痕量,而在肾脏、心脏和脑组织中主要为二酮结构的氧化加合物。以及在尿液和粪便中。这些结果表明,芦丁摄入后立即形成的未氧化的芦丁-MGO加合物可能容易被氧化,最终以氧化形式沉积在组织中并排出体外。结果表明,6-(1-乙酰醇)-8-(1-乙酰醇)-芦丁的形成可显著降低MGO对人胃上皮细胞(GES-1)、人结肠癌细胞(Caco-2)和人脐静脉内皮细胞(HUVEC)的细胞毒性,表明芦丁有可能作为一种安全有效的MGO清除剂、解毒剂和AGEs抑制剂。
Methylglyoxal (MGO) is a highly reactive precursor which forms advanced glycation end-products (AGEs) in vivo, which lead to metabolic syndrome and chronic diseases. It is also a precursor of various carcinogens, including acrylamide and methylimidazole, in thermally processed foods. Rutin could efficiently scavenge MGO by the formation of various adducts. However, the metabolism and safety concerns of the derived adducts were paid less attention to. In this study, the optical isomers of di-MGO adducts of rutin, namely 6-(1-acetol)-8-(1-acetol)-rutin, were identified in foods and in vivo. After oral administration of rutin (100 mg/kg BW), these compounds reached the maximum level of 15.80 μg/L in plasma at 15 min, and decreased sharply under the quantitative level in 30 min. They were detected only in trace levels in kidney and fecal samples, while their corresponding oxidized adducts with dione structures presented as the predominant adducts in kidney, heart, and brain tissues, as well as in urine and feces. These results indicated that the unoxidized rutin-MGO adducts formed immediately after rutin ingestion might easily underwent oxidation, and finally deposited in tissues and excreted from the body in the oxidized forms. The formation of 6-(1-acetol)-8-(1-acetol)-rutin significantly mitigated the cytotoxicity of MGO against human gastric epithelial (GES-1), human colon carcinoma (Caco-2), and human umbilical vein endothelial (HUVEC) cells, which indicated that rutin has the potential to be applied as a safe and effective MGO scavenger and detoxifier, and AGEs inhibitor.
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