Cereulide Exposure Caused Cytopathogenic Damages of Liver and Kidney in Mice

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 mu g/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 1 alpha (IRE1 alpha)/Xbox binding protein (XBP1) and PRKR-like ER kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2 alpha), 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 IRE1 alpha/XBP1 and PERK/eIF2 alpha 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.

Automated summary

Long-term exposure to Cereulide causes oxidative stress in liver and kidney tissues, leading to activation of ER stress pathways and ultimately apoptosis and tissue damage. Inhibition of these pathways can reduce the toxic effects of this toxin.