5-HMF induces anaphylactoid reactions in vivo and in vitro

Encan Li; Ni Lin; Ruirui Hao; Xiaoyu Fan; Lin Lin; Guang Hu; Sheng Lin; Jiuming He; Qingfen Zhu; Hongtao Jin

doi:10.1016/j.toxrep.2020.10.010

5-HMF induces anaphylactoid reactions in vivo and in vitro

Toxicol Rep. 2020 Oct 16:7:1402-1411. doi: 10.1016/j.toxrep.2020.10.010. eCollection 2020.

Authors

Encan Li¹, Ni Lin², Ruirui Hao¹, Xiaoyu Fan¹, Lin Lin¹, Guang Hu¹, Sheng Lin³, Jiuming He³, Qingfen Zhu⁴, Hongtao Jin^{1

5}

Affiliations

¹ New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
² 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.
³ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
⁴ Shandong Institute for Food and Drug Control, Jinan, 250101, China.
⁵ Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., Beijing, 100050, China.

Abstract

Aim: 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.

Methods: We investigated anaphylactoid reactions in Brown Norway (BN) rats and Institute of Cancer Research (ICR) mice to identify 5-HMF mediated in vivo 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.

Results: 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.

Conclusions: Our findings suggest that 5-HMF induces anaphylactoid reactions both in vivo and in vitro, therefore 5-HMF limits in sugar-containing products should receive more regulatory attention.

Keywords: 5-HMF; Anaphylactoid reaction; Degranulation; Immunotoxicity; In vitro and in vivo animal models.