Cellular Effects of T-2 Toxin on Primary Hepatic Cell Culture Models of Chickens

Mackei, Máté; Orbán, Kata; Molnár, Andor; Pál, László; Dublecz, Károly; Húsvéth, Ferenc; Neogrády, Zsuzsanna; Mátis, Gábor

doi:10.3390/toxins12010046

Cited by 20 publications

(15 citation statements)

References 41 publications

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“…In the present study, based on the results of the CCK-8 assay, the aerobe catabolic activity of the cultured cells moderately decreased after applying both inhibitors MI432 and MI460 in certain concentrations for 4 h. However, the extent of the reduction indicated that the inhibitors were not cytotoxic, in line with a previous study in which T-2 toxin caused a similar decline in the metabolic activity of the same cell culture models without being cytotoxic [ 25 ]. Following the longer, 24 h incubation, no significant differences were observed between control and MI-treated cells anymore, suggesting the rapid metabolic adaptation of liver cells to the applied MIs.…”

Section: Discussionsupporting

confidence: 89%

The Effects of Matriptase Inhibition on the Inflammatory and Redox Homeostasis of Chicken Hepatic Cell Culture Models

et al. 2021

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The function of the transmembrane serine protease matriptase is well described in mammals, but it has not been elucidated in avian species yet. Hence, the aim of the present study was to assess the effects of the 3-amidinophenylalanine (3-AphA)-type matriptase inhibitors MI432 and MI460 on the inflammatory and oxidative state of chicken primary hepatocyte mono-cultures and hepatocyte–nonparenchymal cell co-cultures, the latter serving as a proper model of hepatic inflammation in birds. Cell cultures were exposed to MI432 and MI460 for 4 and 24 h at 10, 25, and 50 µM concentrations, and thereafter the cellular metabolic activity, extracellular interleukin (IL-)6, IL-8, H2O2 and malondialdehyde concentrations were monitored. Both inhibitors caused a transient moderate reduction in the metabolic activity following 4 h exposure, which was restored after 24 h, reflecting the fast hepatic adaptation potential to matriptase inhibitor administration. Furthermore, MI432 triggered an intense elevation in the cellular proinflammatory IL-6 and IL-8 production after both incubation times in all concentrations, which was not coupled to enhanced oxidative stress and lipid peroxidation based on unchanged H2O2 production, malondialdehyde levels and glutathione peroxidase activity. These data suggest that physiological matriptase activities might have a key function in retaining the metabolic and inflammatory homeostasis of the liver in chicken, without being a major modulator of the hepatocellular redox state.

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Section: Discussionsupporting

confidence: 89%

The Effects of Matriptase Inhibition on the Inflammatory and Redox Homeostasis of Chicken Hepatic Cell Culture Models

et al. 2021

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“…The major metabolic pathways of T-2 include hydroxylation, hydrolysis, deepoxidation, and conjugation ( Figure 5 ) [ 153 ]. The typical metabolites of T-2 in human and animals are HT-2 toxin (HT-2), neosolaniol (NEO), 3′-OH-T-2, 3′-OH-HT-2, T-2 triol, T-2 tetraol, and some C12,13-deepoxy products [ 99 , 154 ].…”

Section: Biotransformation Of Mycotoxinsmentioning

confidence: 99%

Mycotoxins: Biotransformation and Bioavailability Assessment Using Caco-2 Cell Monolayer

Tran

Viktorová

Ruml

2020

Toxins

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The determination of mycotoxins content in food is not sufficient for the prediction of their potential in vivo cytotoxicity because it does not reflect their bioavailability and mutual interactions within complex matrices, which may significantly alter the toxic effects. Moreover, many mycotoxins undergo biotransformation and metabolization during the intestinal absorption process. Biotransformation is predominantly the conversion of mycotoxins meditated by cytochrome P450 and other enzymes. This should transform the toxins to nontoxic metabolites but it may possibly result in unexpectedly high toxicity. Therefore, the verification of biotransformation and bioavailability provides valuable information to correctly interpret occurrence data and biomonitoring results. Among all of the methods available, the in vitro models using monolayer formed by epithelial cells from the human colon (Caco-2 cell) have been extensively used for evaluating the permeability, bioavailability, intestinal transport, and metabolism of toxic and biologically active compounds. Here, the strengths and limitations of both in vivo and in vitro techniques used to determine bioavailability are reviewed, along with current detailed data about biotransformation of mycotoxins. Furthermore, the molecular mechanism of mycotoxin effects is also discussed regarding the disorder of intestinal barrier integrity induced by mycotoxins.

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“…There is only limited data available related to this issue; however, it would be an essential basis for future studies concerning the in vitro testing of anti-inflammatory agents. The applied 2D primary hepatocyte-non-parenchymal cell co-cultures of chicken origin have already been used in previous studies to investigate the cellular effects of acute heat stress and T-2 toxin [24,44]. Furthermore, even inflammatory models were designed using similar cultures of porcine origin [45].…”

Section: Discussionmentioning

confidence: 99%

Two Sides to Every Question: Attempts to Activate Chicken Innate Immunity in 2D and 3D Hepatic Cell Cultures

Sebők

Tráj

Vörösházi

et al. 2021

Cells

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The liver with resident tissue macrophages is the site of vivid innate immunity, activated also by pathogen-associated molecular patterns (PAMPs) leaking through the intestinal barrier. As gut-derived inflammatory diseases are of outstanding importance in broiler chickens, the present study aimed to establish a proper hepatic inflammatory model by comparing the action of different PAMPs from poultry pathogens on chicken 2D and 3D primary hepatocyte—non-parenchymal cell co-cultures, the latter newly developed with a magnetic bioprinting method. The cultures were challenged by the bacterial endotoxins lipopolysaccharide (LPS) from Escherichia coli, lipoteichoic acid (LTA) from Staphylococcus aureus and by enterotoxin (ETxB) from Escherichia coli, Salmonella Typhimurium derived flagellin, phorbol myristate acetate (PMA) as a model proinflammatory agent and polyinosinic polycytidylic acid (poly I:C) for mimicking viral RNA exposure. Cellular metabolic activity was assessed with the CCK-8 test, membrane damage was monitored with the lactate dehydrogenase (LDH) leakage assay and interleukin-6 and -8 (Il-6 and -8) concentrations were measured in cell culture medium with a chicken specific ELISA. Both LPS and LTA increased the metabolic activity of the 3D cultures, concomitantly decreasing the LDH leakage, while in 2D cultures ETxB stimulated, PMA and poly I:C depressed the metabolic activity. Based on the moderately increased extracellular LDH activity, LTA seemed to diminish cell membrane integrity in 2D and poly I:C in both cell culture models. The applied endotoxins remarkably reduced the IL-8 release of 3D cultured cells, suggesting the effective metabolic adaptation and the presumably initiated anti-inflammatory mechanisms of the 3D spheroids. Notwithstanding that the IL-6 and IL-8 production of 2D cells was mostly not influenced by the endotoxins used, only the higher LTA dose was capable to evoke an IL-8 surge. Flagellin, PMA and poly I:C exerted proinflammatory action in certain concentrations in both 2D and 3D cultures, reflected by the increased cellular IL-6 release. Based on these data, LTA, flagellin, PMA and poly I:C can be considered as potent candidates to induce inflammation in chicken primary hepatic cell cultures, while LPS failed to trigger proinflammatory cytokine production, suggesting the relatively high tolerance of avian liver cells to certain bacterial endotoxins. These results substantiate that the established 3D co-cultures seemed to be proper tools for testing potential proinflammatory molecules; however, the remarkable differences between 2D and 3D models should be addressed and further studied.

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Cellular Effects of T-2 Toxin on Primary Hepatic Cell Culture Models of Chickens

Cited by 20 publications

References 41 publications

The Effects of Matriptase Inhibition on the Inflammatory and Redox Homeostasis of Chicken Hepatic Cell Culture Models

The Effects of Matriptase Inhibition on the Inflammatory and Redox Homeostasis of Chicken Hepatic Cell Culture Models

Mycotoxins: Biotransformation and Bioavailability Assessment Using Caco-2 Cell Monolayer

Two Sides to Every Question: Attempts to Activate Chicken Innate Immunity in 2D and 3D Hepatic Cell Cultures

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