Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets

Abstract

ObjectiveFusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets.MethodsFifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks.ResultsA total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, α-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN.ConclusionIn summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

Zearalenone and the Immune Response

“…By contrast, the weight of the immune organs seems to be less affected by the exposure to ZEA as resulted from the literature data (Table 4), but the toxin has been responsible for immune organs atrophy and depletion as well as for other histopathological modifications in immune organs. ZEA caused also a decrease of B cell percentage in the spleen or swelling of red pulp [57,108,111]. Atrophy of white pulp and swelling of red pulp post-weanling gilts 2.0, 3.2 mg/kg feed 18 days [110] No effect on spleen and bursa of Fabricius weights one-day-old broiler chicks 10-800 mg/kg feed 21 days [113] No effect on spleen and bursa of Fabricius weights one-day -old broiler chicks 50-800 mg/kg feed 3 weeks [114] Enlargement of the spleen in males Sprague Dawley rats 1.25, 3.75 mg/kg b.w.…”

“…By contrast, the weight of the immune organs seems to be less affected by the exposure to ZEA as resulted from the literature data ( Table 4 ), but the toxin has been responsible for immune organs atrophy and depletion as well as for other histopathological modifications in immune organs. ZEA caused also a decrease of B cell percentage in the spleen or swelling of red pulp [ 57 , 108 , 111 ].…”

Colon Microbiome of Pigs Fed Diet Contaminated with Commercial Purified Deoxynivalenol and Zearalenone

“…ZEN also shows numerous genotoxic and cytotoxic effects in vitro and ex vivo, and is potentially carcinogenic [ 14 ]. Further, ZEN is recognized to be immunotoxic; nonetheless, its function in the inflammatory response is not yet completely understood [ 15 ].…”

Combinational Inhibitory Action of Hedychium spicatum L. Essential Oil and γ-Radiation on Growth Rate and Mycotoxins Content of Fusarium graminearum in Maize: Response Surface Methodology

“…Several studies have addressed the toxic effects of DON and ZEA in in-vitro and in-vivo experiments and documented their genotoxicity, hepatotoxicity, neurotoxicity, immunotoxicity, nephrotoxicity, reproductive, and developmental toxicity, carcinogenicity, etc. (Zinedine et al, 2007 ; Venkataramana et al, 2014 ; Schumann et al, 2016 ; Kalagatur et al, 2017 ; Gonçalves et al, 2018 ; Muthulakshmi et al, 2018 ; Reddy et al, 2018 ). Moreover, International Agency for Research on Cancer (IARC) has studied the carcinogenic property of DON and ZEA in laboratory animals and classified as the group 3 carcinogens (IARC, 1999 ).…”