Proanthocyanidins Protect Epithelial Cells from Zearalenone-Induced Apoptosis via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis Pathways in Mouse Small Intestines

Miao Long,Jianbin He,Xinliang Chen,Mingyang Wang,Peng Li,Nan Wang,Shuhua Yang,Jingjing Tong,Jiawen Pan

doi:10.3390/molecules23071508

Miao Long, Jianbin He + Show 7 more

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https://doi.org/10.3390/molecules23071508

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Abstract

This study evaluated the protective effect of proanthocyanidins (PCs) on reducing apoptosis in the mouse intestinal epithelial cell model MODE-K exposed to zearalenone (ZEA) through inhibition of the endoplasmic reticulum stress (ERS)-induced apoptosis pathway. Our results showed that PCs could reduce the rate of apoptosis in MODE-K cells exposed to ZEA (p < 0.01). PCs significantly increased the ZEA-induced antioxidant protective effects on the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on the content of GSH. PCs also significantly decreased the ZEA-induced increase in the content of malondialdehyde (MDA). The analysis indicated that ZEA increased both mRNA and protein expression levels of C/EBP homologous protein (CHOP), GRP78, c-Jun N-terminal kinase (JNK), and cysteinyl aspartate specific proteinase 12 (caspase-12) (p < 0.05), which are related to the ERS-induced apoptosis pathway. ZEA decreased levels of the pro-apoptotic related protein Bcl-2 (p < 0.05) and increased the anti-apoptotic related protein Bax (p < 0.05). Co-treatment with PCs was also shown to significantly reverse the expression levels of these proteins in MODE-K cells. The results demonstrated that PCs could protect MODE-K cells from oxidative stress and apoptosis induced by ZEA. The underlying mechanism may be that PCs can alleviate apoptosis in mouse intestinal epithelial cells by inhibition of the ERS-induced apoptosis pathway.

Highlights

The gastrointestinal tract (GIT) is the primary tissue site of interactions with food contaminants [1].Various toxic substances such as mycotoxins, which often exist in contaminated food or feeds, can damage intestinal epithelial cells [2]
The results were consistent with our previous findings that PCs affected the growth of OurOur results further confirmed that inthat an appropriate concentration range, PCs results further confirmed in an appropriate concentration range, PCs had growth-promoting effects, and when the maximum concentration range was exceeded, this couldthis could had growth-promoting effects, and when the maximum concentration range was exceeded, cause cytotoxicity [42,43,44]
As ZEA can induce apoptosis by causing oxidative stress and because PCs have a strong antioxidant capability, we aimed to determine whether PCs can prevent intestinal epithelial cell apoptosis induced by ZEA

Summary

Introduction

The gastrointestinal tract (GIT) is the primary tissue site of interactions with food contaminants [1]. Various toxic substances such as mycotoxins, which often exist in contaminated food or feeds, can damage intestinal epithelial cells [2]. ZEA has shown multiple toxicities in the immune system [6], liver [7], and kidney [8]. It has carcinogenic potential [9] and enhances lipid peroxidation [10], which are most likely a result of its oxidative stress properties [11,12]

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