Wild Raspberry Subjected to Simulated Gastrointestinal Digestion Improves the Protective Capacity against Ethyl Carbamate-Induced Oxidative Damage in Caco-2 Cells.

Wei Chen,Yang Xu,Ya Li,Lingxia Zhang,Xiaodong Zheng

doi:10.1155/2016/3297363

Abstract

Ethyl carbamate (EC), a probable human carcinogen, occurs widely in many fermented foods. Previous studies indicated that EC-induced cytotoxicity was associated with oxidative stress. Wild raspberries are rich in polyphenolic compounds, which possess potent antioxidant activity. This study was conducted to investigate the protective effect of wild raspberry extracts produced before (RE) and after in vitro simulated gastrointestinal digestion (RD) on EC-induced oxidative damage in Caco-2 cells. Our primary data showed that ethyl carbamate could result in cytotoxicity and genotoxicity in Caco-2 cells and raspberry extract after digestion (RD) may be more effective than that before digestion (RE) in attenuating toxicity caused by ethyl carbamate. Further investigation by fluorescence microscope revealed that RD may significantly ameliorate EC-induced oxidative damage by scavenging the overproduction of intracellular reactive oxygen species (ROS), maintaining mitochondrial function and preventing glutathione (GSH) depletion. In addition, HPLC-ESI-MS results showed that the contents of identified polyphenolic compounds (esculin, kaempferol O-hexoside, and pelargonidin O-hexoside) were remarkably increased after digestion, which might be related to the better protective effect of RD. Overall, our results demonstrated that raspberry extract undergoing simulated gastrointestinal digestion may improve the protective effect against EC-induced oxidative damage in Caco-2 cells.

Highlights

Ethyl carbamate (EC) was initially identified as a carcinogen to animals in the 1940s and subsequently classified as a group 2A carcinogen that is probably carcinogenic to humans by IARC, a World Health Organization’s International Agency for Research on Cancer [1]
Considering the genotoxicity generated by dietary EC exposure, the minor groove binder Hoechst 33258, which is known to sensitively bind the adenine-thymine rich sites of DNA, was used to detect the genotoxicity induced in Caco-2 cells and to evaluate the effect of raspberry extracts produced before (RE) or raspberry digesta (RD) on EC-induced genotoxicity
The present study, for the first time, revealed that EC induced excessive production of intracellular reactive oxygen species (ROS), accelerated GSH depletion and caused mitochondrial dysfunction, which resulted in disturbed cellular redox balance and oxidative damage in Caco-2 cells

Summary

Introduction

Ethyl carbamate (EC) was initially identified as a carcinogen to animals in the 1940s and subsequently classified as a group 2A carcinogen that is probably carcinogenic to humans by IARC, a World Health Organization’s International Agency for Research on Cancer [1]. It was noticeable that ethyl carbamate was detected in many fermented foods, in yeast breads and alcoholic beverages [2]. The formation of EC in those fermented foods was based on the reaction between ethanol and nitrogen-containing compounds such as urea and citrulline [3]. Recent studies carried out in mice have revealed that frequent exposure to EC may cause genotoxicity and cytotoxicity and even leads to cancer development [4,5,6]. Potential harm of EC on human health cannot be neglected

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Results

Conclusion