Cereulide Exposure Caused Cytopathogenic Damages of Liver and Kidney in Mice

  • Int J Mol Sci. 2021 Aug 24;22(17):9148. doi: 10.3390/ijms22179148.
Danyang Li  1  2  3 ,  Ruqin Lin  1  2  3 ,  Yangyang Xu  1  2  3 ,  Qingmei Chen  1  2  3 ,  Fengru Deng  1  2  3 ,  Yiqun Deng  1  2  3 ,  Jikai Wen  1  2  3
Affiliations
  • 1. Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
  • 2. Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China.
  • 3. Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China.
PMID: 34502057 DOI: 10.3390/ijms22179148
Abstract

Cereulide is one of the main food-borne toxins for vomiting synthesized by Bacillus cereus, and it widely contaminates meat, eggs, milk, and starchy foods. However, the toxicological effects and mechanisms of the long-time exposure of cereulide in vivo remain unknown. In this study, oral administration of 50 and 200 μg/kg body weight cereulide in the mice for 28 days caused oxidative stress in liver and kidney tissues and induce abnormal expression of inflammatory factors. In pathogenesis, cereulide exposure activated endoplasmic reticulum stress (ER stress) via the pathways of inositol-requiring enzyme 1α (IRE1α)/Xbox binding protein (XBP1) and PRKR-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α), and consequently led to the Apoptosis and tissue damages in mouse liver and kidney. In vitro, we confirmed that the accumulation of Reactive Oxygen Species (ROS) caused by cereulide is the main factor leading to ER stress in HepaRG and HEK293T cells. Supplementation of sodium butyrate (NaB) inhibited the activations of IRE1α/XBP1 and PERK/eIF2α pathways caused by cereulide exposure in mice, and reduced the cell Apoptosis in liver and kidney. In conclusion, this study provides a new insight in understanding the toxicological mechanism and prevention of cereulide exposure.

Keywords
apoptosis; cereulide; endoplasmic reticulum stress; reactive oxygen species; sodium butyrate.
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