Abstract

Acrylamide (AA), is an important contaminant formed during food processing under high temperature. Due to its potential neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity effects, this food contaminant has been recognized as a human health concern. Previous studies showed that acrylamide-induced toxicity is associated with active metabolite of acrylamide by cytochrome P450 enzyme, oxidative stress, mitochondrial dysfunction and DNA damage. In the current study, we investigated the role of oxidative stress in acrylamide's genotoxicity and therapeutic potential role of ellagic acid (EA) in human lymphocytes. Human lymphocytes were simultaneously treated with different concentrations of EA (10, 25 and 50 μM) and acrylamide (50 μM) for 4 h at 37°C. After 4 hours of incubation, the toxicity parameters such cytotoxicity, ROS formation, oxidized/reduced glutathione (GSH/GSSG) content, malondialdehyde (MDA) level, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were analyzed using biochemical and flow cytometry evaluations. It has been found that acrylamide (50 μM) significantly increased cytotoxicity, ROS formation, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage in human lymphocytes. On the other hand, cotreatment with EA (25 and 50 μM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the cytotoxicity, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage. Together, these results suggest that probably the co-exposure of EA with foods containing acrylamide could decrease mitochondrial, lysosomal and DNA damages, and oxidative stress induced by acrylamide in human body.

Highlights

  • One of heat-induced toxic substances in during food processing techniques is acrylamide (AA) that has recently received much scientific interest [1]

  • ellagic acid (EA) mitigated the ROS formation induced by acrylamide in isolated lymphocytes To measure the effect of EA on acrylamide-induced oxidative stress in isolated lymphocytes, the level of ROS was measured through DCFH-DA fluorescence by flow cytometry

  • Our results showed that acrylamide induce DNA damage in human lymphocytes, these results are consistent with previously published data

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Summary

Introduction

One of heat-induced toxic substances in during food processing techniques is acrylamide (AA) that has recently received much scientific interest [1]. Due to wide range of acrylamide exposure sources diet, drinking water, smoking, and environmental/occupational sources, many people can be exposed to this chemical through oral, dermal or inhalation [1,5,6]. Acrylamide is associated with a wide range of different toxicities in human and animal such as neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity [9]. This substance has been categorized as a probable human carcinogen by the International Agency for Research on Cancer (IARC) [10]. Due to definite exposure of humans to acrylamide for various sources, probably detoxification of this compound inside the body can be a suitable approach to reduce its toxicity. Natural compounds with antioxidant and antitumorigenic properties can probably play a promising role in inhibiting the toxicity caused by acrylamide

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