Walnut Polyphenol Extract Protects against Malathion- and Chlorpyrifos-Induced Immunotoxicity by Modulating TLRx-NOX-ROS.

Fengjun Wang,Ao Zhang,Yue Zhao,Meiyu Xu,Yue Zhang,Qiang Weng,Chang Fan

doi:10.3390/nu12030616

Abstract

Malathion (MT) and chlorpyrifos (CPF) are immunotoxic organophosphate pesticides that are used extensively in agriculture worldwide. Dietary polyphenols protect against a variety of toxins. In this study, walnut polyphenol extract (WPE) prevents MT- or CPF-induced toxicity to splenic lymphocytes in vitro. WPE promotes the proliferation of MT-exposed splenocytes, as indicated by increases in the proportions of splenic T-lymphocyte subpopulations (CD3+, CD4+, and CD8+ T cells) and levels of T-cell-related cytokines interleukin (IL)-2, interferon-γ, IL-4, and granzyme B, and decreases the apoptosis-associated proteins Bax and p53. WPE also significantly enhances the proliferation of CPF-exposed splenic B lymphocytes (CD19+ B cells) and levels of the B-cell-related cytokine IL-6, leading to decreases of the apoptosis-associated proteins Bax and p53. These effects are related to reduced production of reactive oxygen species (ROS), as evidenced by normalized hydroxyl radical (•OH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione (GSH) levels, which are associated with decreased expression of NADPH oxidase 2 (NOX2) and dual oxidase 1 (DUOX1). WPE inhibits the production of ROS and expression of NOX by regulating toll-like receptors 4 and 7 in MT- and CPF-exposed splenic lymphocytes. In conclusion, WPE protects against MT- or CPF-mediated immunotoxicity and inhibits oxidative damage by modulating toll-like receptor (TLR)x-NOX-ROS.

Highlights

Malathion (MT) O,O-dimethyl-S-1,2-dicarboethoxy-ethyl-dithiophosphate, one of the most widely used organophosphate pesticides, is distributed extensively in the environment
Splenocytes exposed to MT or CPF were subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay to assess the effects of walnut polyphenol extract (WPE) on their viability
To determine whether WPE inhibits the overproduction of reactive oxygen species (ROS) through NADPH oxidase complexes (NOX), we evaluated the expression of NADPH oxidase 2 (NOX2) and dual oxidase 1 (DUOX1) in splenic lymphocytes treated with MT or CPF alone or in combination with WPE

Summary

Introduction

Malathion (MT) O,O-dimethyl-S-1,2-dicarboethoxy-ethyl-dithiophosphate, one of the most widely used organophosphate pesticides, is distributed extensively in the environment. O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)-phosphorothioate is an organophosphate pesticide used in agriculture that causes neurotoxicity, reproductive toxicity, respiratory toxicity, hepatotoxicity, and oxidative stress [2,3]. MT and CPF induce immunotoxicity in chicks and rats [3,4,5]. MT alters populations of CD4+ and CD8+ T lymphocytes and the production of interferon (IFN)-γ and interleukin (IL)-4 in rat spleen [3]. CPF suppresses splenic cell proliferation and cytokine production in rats and reduces IFN-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels in mice [5]. It is important to note that MT and CPF induce overproduction of reactive oxygen species (ROS), resulting in oxidative stress [6,7]

Results

Discussion

Conclusion