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呋塞米的体外/体内毒理学研究及相关机制探讨。

Toxicology studies of furosine in vitro/in vivo and exploration of the related mechanism.

机构信息

Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, People's Republic of China.

Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, People's Republic of China.

出版信息

Toxicol Lett. 2018 Jul;291:101-111. doi: 10.1016/j.toxlet.2018.02.018. Epub 2018 Feb 16.

DOI:10.1016/j.toxlet.2018.02.018
PMID:29458171
Abstract

AIM

Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively.

METHODS

In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored. In vivo, the acute toxicity studieswere performed, organ index, hematology parameters, functions of liver/kidney and pathological changes were detected and the target organs were uncovered.

RESULTS

Hek293 cells and HepG2 cells were themost sensitive to furosine with respect to cytotoxicity and apoptosis. Furosine inhibited mice weight gain, and affected the functions of liver and kidney.

CONCLUSIONS

Furosine posed toxic effects on mice liver and kidney, suggested thatthey were the target organs for furosine toxicity. This study for the first time provides evidence that high dosages of furosine pose adverse biological effects on the health of animals through induction of cell apoptosis and activation of inflammatory necrosis response.

摘要

目的

呋塞米是美拉德反应产物(MRPs)之一,存在于多种热加工食品中。但其毒性仍不清楚。本研究旨在分别在细胞模型和 CD-1 小鼠中评估呋塞米的毒性。

方法

体外检测呋塞米对细胞活力、细胞周期和凋亡(Hek293、HepG2、SK-N-SH 和 Caco2)的影响,并进行评价,确定敏感细胞系和进一步动物实验的合适呋塞米剂量,并探讨毒性机制。体内进行急性毒性研究,检测器官指数、血液学参数、肝/肾功能以及组织病理学变化,揭示靶器官。

结果

Hek293 细胞和 HepG2 细胞对呋塞米的细胞毒性和凋亡最敏感。呋塞米抑制小鼠体重增加,并影响肝肾功能。

结论

呋塞米对小鼠的肝、肾有一定的毒性作用,提示肝、肾是呋塞米毒性的靶器官。本研究首次提供证据表明,高剂量的呋塞米通过诱导细胞凋亡和激活炎症坏死反应,对动物的健康产生不良的生物学影响。

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