Abstract

Simple SummaryMycotoxins are toxic secondary metabolites of fungi that frequently contaminate animal feed and human food in different combinations; therefore, it is of great importance to determine the effects of mycotoxin co-contamination. Pigs are one of the most sensitive animal species to Fusarium mycotoxins, and the liver is an important site of mycotoxin metabolism. The objective of the present research was to determine histopathological changes, apoptosis, and proliferation in the liver of gilts fed with Fusarium mycotoxin-contaminated feed for a prolonged time at the end of their pregnancy and until weaning of their piglets. Additionally, the same parameters were evaluated in the liver of their piglets to determine whether Fusarium mycotoxins would affect the offspring. The results revealed increased hepatocellular necrosis and apoptosis as well as sinusoidal leukocytosis with inflammatory infiltrates of hepatic lobules in experimental gilts, but no significant changes were observed in the piglet livers, implying that the utilized concentrations and duration of exposure did not cause detrimental effects on them. Interestingly, the amount of interlobular connective tissue in the liver of experimental gilts was significantly decreased. The obtained results emphasized the need to evaluate Fusarium mycotoxin concentrations in feed because even at low concentrations, they can cause adverse effects, but there is less concern for severe detrimental effects on the offspring.Mycotoxins are common fungal secondary metabolites in both animal feed and human food, representing widespread toxic contaminants that cause various adverse effects. Co-contamination with different mycotoxins is frequent; therefore, this study focused on feed contaminated with Fusarium mycotoxins, namely, deoxynivalenol (5.08 mg/kg), zearalenone (0.09 mg/kg), and fusaric acid (21.6 mg/kg). Their effects on the liver of gilts and their piglets were chosen as the research subject as pigs are one of the most sensitive animal species that are also physiologically very similar to humans. The gilts were fed the experimental diet for 54 ± 1 day, starting late in their pregnancy and continuing until roughly a week after weaning of their piglets. Livers of gilts and their piglets were assessed for different histopathological changes, apoptosis, and proliferation activity of hepatocytes. On histopathology, gilts fed the experimental diet had a statistically significant increase in hepatocellular necrosis and apoptosis (p = 0.0318) as well as sinusoidal leukocytosis with inflammatory infiltrates of hepatic lobules (p = 0.0004). The amount of interlobular connective tissue in the liver of experimental gilts was also significantly decreased (p = 0.0232), implying a disruption in the formation of fibrous connective tissue. Apoptosis of hepatocytes and of cells in hepatic sinusoids, further assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, showed a statistically significant increase (p = 0.0224 and p = 0.0007, respectively). No differences were observed in piglet livers. These results indicated that Fusarium mycotoxins elicited increased apoptosis, necrosis, and inflammation in the liver of gilts, but caused no effects on the liver of piglets at these concentrations.

Highlights

  • Mycotoxins are toxic secondary metabolites produced by many filamentous fungi.The most important fungi causing frequent and problematic contamination of human food and animal feed belong to the fungal genera of Fusarium, Aspergillus, and Penicillium

  • Seven assessed histopathological changes were observed on hematoxylin and eosin (H&E)-stained liver sections: fibrosis, sinusoidal leukocytosis with inflammatory infiltrates of hepatic lobules, portal tract inflammatory infiltrates, hepatocytes with vacuolar or granular cytoplasm, hepatocellular necrosis and apoptosis, hepatocellular megalocytosis, and hepatocellular megakaryosis

  • Overt fibrosis was only observed in the liver of one gilt from the control group, but even this was mild based on its final score of 1 and was not statistically significant in comparison with the experimental group (p = 0.3681)

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Summary

Introduction

Mycotoxins are toxic secondary metabolites produced by many filamentous fungi.The most important fungi causing frequent and problematic contamination of human food and animal feed belong to the fungal genera of Fusarium, Aspergillus, and Penicillium. The most toxicologically important Fusarium toxins are fumonisins (FBs), zearalenone (ZEN), and trichothecenes, such as deoxynivalenol (DON), nivalenol (NIV), diacetoxyscirpenol (DAS), and T-2 toxin [3]. Both in vitro and in vivo studies have demonstrated that toxicokinetics, bioavailability, and the mechanisms of action of these substances vary depending on the species involved [4]. One of them is fusaric acid (FA), which is found in several types of cereal grain and mixed feeds This mycotoxin needs to be further investigated in vitro and in vivo because its neurochemical effects and possible synergistic effects with other mycotoxins, especially DON and FBs, may pose a problem to humans and livestock [7]

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