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暴露于多种有害美拉德反应产物组合对 Sprague-Dawley 大鼠的代谢干扰和健康影响。

Metabolic perturbations and health impact from exposure to a combination of multiple harmful Maillard reaction products on Sprague-Dawley rats.

机构信息

College of Food Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.

出版信息

Food Funct. 2022 May 23;13(10):5515-5527. doi: 10.1039/d2fo00143h.

DOI:10.1039/d2fo00143h
PMID:35522130
Abstract

The present study aimed to investigate the metabolic perturbations and health impact of the co-accumulation of Maillard reaction products (MRPs), including acrylamide, harmane, and -(carboxymethyl)lysine (CML), serum biochemical and histopathological examinations as well as metabolomic analysis. Sprague-Dawley rats were treated with acrylamide (2 mg per kg body weight [bw]), harmane (1 mg per kg bw), CML (2 mg per kg bw), and combinations of these MRPs. Harmane did not cause adverse effects on the health of rats, whereas acrylamide and CML resulted in significantly ( < 0.05) decreased insulin sensitivity (HOMA-IR > 1), increased oxidative stress levels, and pathological injuries to the pancreas, liver, and gastrocnemius. Owing to the antioxidant and anti-diabetic activities of harmane, the effects of the combination of the MRPs on oxidative stress levels, blood glucose metabolism, and pathological injuries to the pancreas and gastrocnemius were relieved. However, new health problems, including pathological injury of the kidneys and increased cancer risk, were observed. Metabolomic analysis revealed that this may be related to the effects of MRPs on the arginine biosynthesis pathway, which resulted in the abnormal metabolism of fumaric acid and the tricarboxylic acid cycle. These results indicated that the mechanisms of the combined effect of MRPs and their effects on health cannot be predicted from the effects of individual MRPs.

摘要

本研究旨在探讨美拉德反应产物(MRPs),包括丙烯酰胺、哈尔满和羧甲基赖氨酸(CML)的共同蓄积对代谢紊乱和健康的影响,通过血清生化和组织病理学检查以及代谢组学分析来评估。使用丙烯酰胺(2 毫克/千克体重[bw])、哈尔满(1 毫克/千克 bw)、CML(2 毫克/千克 bw)以及这些 MRPs 的组合处理 Sprague-Dawley 大鼠。哈尔满对大鼠的健康没有产生不良影响,而丙烯酰胺和 CML 导致胰岛素敏感性显著降低(HOMA-IR > 1),氧化应激水平升高,胰腺、肝脏和比目鱼肌出现病理损伤。由于哈尔满具有抗氧化和抗糖尿病活性,MRPs 组合对氧化应激水平、血糖代谢以及胰腺和比目鱼肌的病理损伤的影响得到缓解。然而,新的健康问题,包括肾脏病理损伤和癌症风险增加,被观察到。代谢组学分析表明,这可能与 MRPs 对精氨酸生物合成途径的影响有关,导致富马酸和三羧酸循环的异常代谢。这些结果表明,MRPs 联合作用的机制及其对健康的影响不能从单个 MRPs 的影响来预测。

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