HMF causes anaphylactic symptoms by acting as a H1 receptor agonist

Biochem Pharmacol. 2020 Jul:177:114008. doi: 10.1016/j.bcp.2020.114008. Epub 2020 Apr 30.

Abstract

5-Hydroxymethylfurfural (HMF) can readily form by acid-catalyzed transformations of various sugars such as fructose, sucrose and to a lesser degree glucose, and is known to widely exist in various sugar-containing consumer products. Thus the potential health effect of HMF has been a subject of intensive studies. There have been earlier reports of HMF's undesirable effects at or above high micromolar concentrations. In this study, HMF is found to stimulate the H1 receptor in vivo and in vitro. When assessed in cell culture and animal models, HMF was found to cause deformation of in cell culture studies of HUVECs at 50 μM, to increase the vascular permeability of paw skin at 1.0 mg/mL, and trigger symptoms of anaphylaxis in animal models at 32.5 μg/kg. At the molecular level, HMF was found to induce the release of NO and related cytokines, and trigger H1 receptor-mediated inflammatory responses. Mutation studies also suggest the binding sites for HMF on the H1 receptor. The findings described suggest the need for close monitoring of HMF contents in consumer products and their related side effects.

Keywords: 5-Hydroxymethylfurfural; Anaphylaxis; H(1) receptor; Histamine; Inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / chemically induced*
  • Animals
  • Cytokines / metabolism
  • Edema / chemically induced
  • Epoprostenol / metabolism
  • Furaldehyde / analogs & derivatives*
  • Furaldehyde / chemistry
  • Furaldehyde / metabolism
  • Furaldehyde / toxicity
  • Hindlimb
  • Histamine / metabolism
  • Histamine Agonists / toxicity
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Mutation
  • Nitric Oxide / metabolism
  • Receptors, Histamine H1 / chemistry
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / metabolism*
  • Surface Plasmon Resonance

Substances

  • Cytokines
  • Histamine Agonists
  • Receptors, Histamine H1
  • Nitric Oxide
  • 5-hydroxymethylfurfural
  • Histamine
  • Epoprostenol
  • Furaldehyde