Abstract

Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious “antagonistic effect” in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB)/globulin (GLO), reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an “antagonistic effect” on liver metabolism of mice.

Highlights

  • During environmental mycotoxin exposure, humans and animals most often encounter mixtures of toxins, rather than single toxins, such as deoxynivalenol (DON) and zearalenone (ZEN) [1].Deoxynivalenol (DON)—a representative mycotoxin of the trichothecene B group—is one of the Toxins 2017, 9, 28; doi:10.3390/toxins9010028 www.mdpi.com/journal/toxinsToxins 2017, 9, 28 most widespread cereal contaminants worldwide [2]

  • Individual DON and ZEN exposure caused a significant increase in enzyme activities of serum alkaline phosphatase (ALP) and alanine transaminase (ALT), which were decreased to normal levels in the 3combined

  • Biosynthesis, and the metabolism of many important chemicals such as galactose, starch, sucrose, this complexity can dilute small metabolic changes from a specific part of the body, and in fructose, mannose, pyruvate fatty acid, valine, leucine and isoleucine. These findings suggested that these cases, tissues may be appropriate for knowledge discovery

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Summary

Introduction

Humans and animals most often encounter mixtures of toxins, rather than single toxins, such as deoxynivalenol (DON) and zearalenone (ZEN) [1].Deoxynivalenol (DON)—a representative mycotoxin of the trichothecene B group—is one of the Toxins 2017, 9, 28; doi:10.3390/toxins9010028 www.mdpi.com/journal/toxinsToxins 2017, 9, 28 most widespread cereal contaminants worldwide [2]. Humans and animals most often encounter mixtures of toxins, rather than single toxins, such as deoxynivalenol (DON) and zearalenone (ZEN) [1]. The trichothecene DON and its derivatives disrupt normal cell function by binding to the ribosome and inhibiting protein synthesis, and by activating cellular kinases involved in signal transduction [6]. Proteome and phosphoproteome strategies were conducted for the interpretation of ribosome functions as a potential platform for spatiotemporal regulation of translation inhibition and ribotoxic stress response caused by DON [7]. DON could induce glucose-regulated protein 78 (GRP78) degradation and it evokes an endoplasmic reticulum stress response that could contribute, in part, to DON-induced interleukin-6 gene expression [9]

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