Abstract

4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC), two important components of vehicle emissions, have been shown to confer toxicity in splenocytes. Certain natural products, such as those derived from walnuts, exhibit a range of antioxidative, antitumor, and anti-inflammatory properties. Here, we investigated the effects of walnut polyphenol extract (WPE) on immunotoxicity induced by PP and PNMC in murine splenic lymphocytes. Treatment with WPE was shown to significantly enhance proliferation of splenocytes exposed to PP or PNMC, characterized by increases in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD4+ and CD8+ T cells), as well as the production of T cell-related cytokines and granzymes (interleukin-2, interleukin-4, and granzyme-B) in cells exposed to PP or PNMC. These effects were associated with a decrease in oxidative stress, as evidenced by changes in OH, SOD, GSH-Px, and MDA levels. The total phenolic content of WPE was 34,800 ± 200 mg gallic acid equivalents/100 g, consisting of at least 16 unique phenols, including ellagitannins, quercetin, valoneic acid dilactone, and gallic acid. Taken together, these results suggest that walnut polyphenols significantly attenuated PP and PNMC-mediated immunotoxicity and improved immune function by inhibiting oxidative stress.

Highlights

  • Vehicle emissions have been shown to significantly inhibit endocrine [1,2,3], reproductive [4,5,6,7], and immune system [8,9] function through a variety of different mechanisms

  • Splenocyte cells exposed to PP or PNMC were examined by MTT assay to assess the effect of walnut polyphenol extract (WPE) on cell viability

  • PP and PNMC significantly decreased cell viability to 66% and 88%, respectively, relative to controls. These effects were significantly attenuated in cells treated with WPE (Figure 1A,B), which limited cytotoxicity in a concentration-dependent manner at concentrations of 0.01–1.0 μg/mL

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Summary

Introduction

Vehicle emissions have been shown to significantly inhibit endocrine [1,2,3], reproductive [4,5,6,7], and immune system [8,9] function through a variety of different mechanisms. Nutrients 2016, 8, 287 in mice [19], inhibited neurological impairments caused by lead exposure in rats [20], and prevented nodularin-mediated lymphocyte toxicity in Carassius auratus [21] Another polyphenol, quercetin, protected against male reproductive toxicity caused by PNMC in germ cells of embryonic chickens and mice [22,23,24], as well as inhibited atrazine-induced damage in the liver, kidney, brain, and heart of adult Wistar rats [25]. Despite these preliminary observations, little is known about the role of these compounds in preventing the immunotoxicity caused by PP or PNMC

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