Cereulide Exposure Caused Cytopathogenic Damages of Liver and Kidney in Mice.

Danyang Li,Ruqin Lin,Fengru Deng,Jikai Wen,Yangyang Xu,Yiqun Deng,Qingmei Chen

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.

Highlights

IntroductionCereulide is a cyclic dodecadepsipeptide toxin, which is synthesized by the foodborne pathogen Bacillus cereus (B. cereus) through a non-ribosomal peptide synthetase system [1]
The body weights in the 50 and 200 μg/kg group were significantly decreased than the control group from day 18 during 28 days of cereulide exposure
The histopathology valuation by hematoxylin and eosin (H&E) staining showed that no apparent pathological changes were occurred in the liver, kidney, and spleen tissue of 10 μg/kg group, which indicated that 10 μg/kg of cereulide was the tolerable daily intake dose in mice

Summary

Introduction

Cereulide is a cyclic dodecadepsipeptide toxin, which is synthesized by the foodborne pathogen Bacillus cereus (B. cereus) through a non-ribosomal peptide synthetase system [1]. In the nature of strong thermal stability and acid resistance, cereulide is difficult to remove from the food chain and detoxified in animal digestive tracts [2,3]. Cereulide food poisoning causes nausea, vomiting and discomfort in mild cases, and liver failure and acute encephalopathy in severe cases [4,5,6]. The part of cereulide ingested with food is rapidly excreted with feces while the part of cereulide toxin is absorbed, passed through intestinal barriers into the blood, and distributed throughout the body [7]. Cereulide exposure aggravates the accumulation of ROS, activates the mitochondrial stress pathway, and causes the release of cytochrome C into the cytoplasm, all of which contribute to cereulide-induced apoptosis [12]

Results

Discussion

Conclusion