Li Encan, Lin Ni, Hao Ruirui, Fan Xiaoyu, Lin Lin, Hu Guang, Lin Sheng, He Jiuming, Zhu Qingfen, Jin Hongtao
New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Beijing Institute for Drug Control, NMPA Key Laboratory for Quality Evaluation of Traditional Chinese Medicine (Traditional Chinese Patent Medicine), Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine, 25 Science Park Road, Changping District, Beijing, 102206, China.
Toxicol Rep. 2020 Oct 16;7:1402-1411. doi: 10.1016/j.toxrep.2020.10.010. eCollection 2020.
Excessive exposure to 5-hydroxymethylfurfural (5-HMF), which is a common impurity in various sugar-containing products, induces serious side effects. Our previous study revealed that 5-HMF exerted immune sensitizing potential when injected into rodents. In this study, we explored 5-HMF mediated anaphylactoid reactions and its underlying molecular mechanisms.
We investigated anaphylactoid reactions in Brown Norway (BN) rats and Institute of Cancer Research (ICR) mice to identify 5-HMF mediated anaphylactoid reactions. RBL-2H3 and P815 cell degranulation models were also established, and degranulation, enzyme-linked immunosorbent, filamentous actin (F-actin) microfilament staining, and western blot assays were performed in these cells.
We showed that 5-HMF induced anaphylactoid reactions by increasing blood vessel permeability in mice, and significantly elevating histamine (His) and glutathione peroxidase-1 (Gpx-1) levels in rat serum. Moreover, after incubation with 5-HMF, β-hexosaminidase (β-Hex), His, IL-4 and IL-6 levels were all significantly increased, thereby inducing cellular degranulation in RBL-2H3 and P815 cells. Finally, 5-HMF also upregulated Lyn, Syk, p38 and JNK protein phosphorylation levels.
Our findings suggest that 5-HMF induces anaphylactoid reactions both i and , therefore 5-HMF limits in sugar-containing products should receive more regulatory attention.
过度暴露于5-羟甲基糠醛(5-HMF)会引发严重的副作用,5-羟甲基糠醛是各种含糖产品中常见的杂质。我们之前的研究表明,将5-HMF注射到啮齿动物体内时具有免疫致敏潜力。在本研究中,我们探讨了5-HMF介导的类过敏反应及其潜在的分子机制。
我们在棕色挪威(BN)大鼠和癌症研究所(ICR)小鼠中研究类过敏反应,以确定5-HMF介导的类过敏反应。还建立了RBL-2H3和P815细胞脱颗粒模型,并在这些细胞中进行脱颗粒、酶联免疫吸附、丝状肌动蛋白(F-肌动蛋白)微丝染色和蛋白质印迹分析。
我们发现5-HMF通过增加小鼠血管通透性诱导类过敏反应,并显著提高大鼠血清中组胺(His)和谷胱甘肽过氧化物酶-1(Gpx-)水平。此外,用5-HMF孵育后,β-己糖胺酶(β-Hex)、His、白细胞介素-4(IL-4)和白细胞介素-6(IL-6)水平均显著升高,从而诱导RBL-2H3和P815细胞发生细胞脱颗粒。最后,5-HMF还上调了Lyn、Syk、p38和JNK蛋白的磷酸化水平。
我们的研究结果表明,5-HMF在体内和体外均可诱导类过敏反应,因此含糖产品中5-HMF的限量应受到更多监管关注。