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

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

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.

Keywords: Cell apoptosis; Furosine; Inflammatory necrosis response; Kidney and liver injury; Toxicity.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Cell Count
  • Caco-2 Cells
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Survival / drug effects
  • Female
  • HEK293 Cells
  • Humans
  • Kidney Function Tests
  • Liver Function Tests
  • Lysine / analogs & derivatives*
  • Lysine / toxicity
  • Male
  • Mice
  • Necrosis
  • Weight Gain / drug effects

Substances

  • furosine
  • Lysine