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Soybean toxin (SBTX) is a protein isolated from soybean seeds and composed of two polypeptide subunits (17 and 27 kDa). SBTX has in vitro activity against phytopathogenic fungi such as Cercospora sojina, Aspergillus niger, and Penicillium herguei, and yeasts like Candida albicans, C. parapsilosis, Kluyveromyces marxiannus, and Pichia membranifaciens. The present study aimed to analyze in vitro whether SBTX causes any side effects on non-target bacterial and mammalian cells that could impede its potential use as a novel antifungal agent. SBTX at 100 μg/mL and 200 μg/mL did not hinder the growth of the bacteria Salmonella enterica (subspecies enterica serovar choleraesuis), Bacillus subtilis (subspecies spizizenii) and Staphylococcus aureus. Moreover, SBTX at concentrations up to 500 μg/mL did not significantly affect the viability of erythrocytes, neutrophils, and human intestinal Caco-2 cells. To study whether SBTX could induce relevant alterations in gene expression, in vitro DNA microarray experiments were conducted in which differentiated Caco-2 cells were exposed for 24 h to 100 μg/mL or 200 μg/mL SBTX. SBTX up-regulated genes involved in cell cycle and immune response pathways, but down-regulated genes that play a role in cholesterol biosynthesis and platelet degranulation pathways. Thus, although SBTX did not affect bacteria, nor induced cytotoxity in mammalian cells, it affected some biological pathways in the human Caco-2 cell line that warrants further investigation.
Mariana Reis Arantes; Ad Peijnenburg; Peter J.M. Hendriksen; Geert Stoopen; Thiago Silva Almeida; Terezinha Maria Souza; Davi Felipe Farias; Ana Fontenele Urano Carvalho; Talita Magalhães Rocha; Luzia Kalyne Almeida Moreira Leal; Ilka Maria Vasconcelos; Jose Tadeu Abreu Oliveira. In vitro toxicological characterisation of the antifungal compound soybean toxin (SBTX). Toxicology in Vitro 2020, 65, 104824 .
AMA StyleMariana Reis Arantes, Ad Peijnenburg, Peter J.M. Hendriksen, Geert Stoopen, Thiago Silva Almeida, Terezinha Maria Souza, Davi Felipe Farias, Ana Fontenele Urano Carvalho, Talita Magalhães Rocha, Luzia Kalyne Almeida Moreira Leal, Ilka Maria Vasconcelos, Jose Tadeu Abreu Oliveira. In vitro toxicological characterisation of the antifungal compound soybean toxin (SBTX). Toxicology in Vitro. 2020; 65 ():104824.
Chicago/Turabian StyleMariana Reis Arantes; Ad Peijnenburg; Peter J.M. Hendriksen; Geert Stoopen; Thiago Silva Almeida; Terezinha Maria Souza; Davi Felipe Farias; Ana Fontenele Urano Carvalho; Talita Magalhães Rocha; Luzia Kalyne Almeida Moreira Leal; Ilka Maria Vasconcelos; Jose Tadeu Abreu Oliveira. 2020. "In vitro toxicological characterisation of the antifungal compound soybean toxin (SBTX)." Toxicology in Vitro 65, no. : 104824.
The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B1 (AFB1), but recovery of total AFB1 is less than 20% when accounting for its conversion to most known metabolites. The aim of this study was to examine the conversion of AFB1 by S9 extracts of BSFL reared on substrates with or without AFB1. Liver S9 of Aroclor-induced rats was used as a reference. To investigate whether cytochrome P450 enzymes are involved in the conversion of AFB1, the inhibitor piperonyl butoxide (PBO) was tested in a number of treatments. The results showed that approximately 60% of AFB1 was converted to aflatoxicol and aflatoxin P1. The remaining 40% of AFB1 was not converted. Cytochrome P450s were indeed responsible for metabolic conversion of AFB1 into AFP1, and a cytoplasmic reductase was most likely responsible for conversion of AFB1 into aflatoxicol.
Nathan Meijer; Geert Stoopen; H.J. Van Der Fels-Klerx; Joop J.A. Van Loon; John Carney; Guido Bosch. Aflatoxin B1 Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts. Toxins 2019, 11, 532 .
AMA StyleNathan Meijer, Geert Stoopen, H.J. Van Der Fels-Klerx, Joop J.A. Van Loon, John Carney, Guido Bosch. Aflatoxin B1 Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts. Toxins. 2019; 11 (9):532.
Chicago/Turabian StyleNathan Meijer; Geert Stoopen; H.J. Van Der Fels-Klerx; Joop J.A. Van Loon; John Carney; Guido Bosch. 2019. "Aflatoxin B1 Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts." Toxins 11, no. 9: 532.
Studies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARα in human liver. Here we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. Quantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. Transcriptomics analysis indicated that 617 genes were upregulated and 665 genes were downregulated by PPARα activation (q value < 0.05). Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. Among the most highly repressed genes upon PPARα activation were several chemokines (e.g. CXCL9-11, CCL8, CX3CL1, CXCL6), interferon γ-induced genes (e.g. IFITM1, IFIT1, IFIT2, IFIT3) and numerous other immune-related genes (e.g. TLR3, NOS2, and LCN2). Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L. Our paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease.
Aafke W.F. Janssen; Bark Betzel; Geert M Stoopen; Frits J. Berends; Ignace M. Janssen; Ad Acm Peijnenburg; Sander Kersten. The impact of PPARα activation on whole genome gene expression in human precision cut liver slices. BMC Genomics 2015, 16, 1 -13.
AMA StyleAafke W.F. Janssen, Bark Betzel, Geert M Stoopen, Frits J. Berends, Ignace M. Janssen, Ad Acm Peijnenburg, Sander Kersten. The impact of PPARα activation on whole genome gene expression in human precision cut liver slices. BMC Genomics. 2015; 16 (1):1-13.
Chicago/Turabian StyleAafke W.F. Janssen; Bark Betzel; Geert M Stoopen; Frits J. Berends; Ignace M. Janssen; Ad Acm Peijnenburg; Sander Kersten. 2015. "The impact of PPARα activation on whole genome gene expression in human precision cut liver slices." BMC Genomics 16, no. 1: 1-13.
Unexpected cholestasis substantially contributes to drug failure in clinical trials. Current models used for safety assessment in drug development do not accurately predict cholestasis in humans. Therefore, it is of relevance to develop new screening models that allow identifying drugs with cholestatic properties.
Ewa Szalowska; Geert Stoopen; Maria J Groot; Peter Jm Hendriksen; Ad Acm Peijnenburg. Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes. BMC Medical Genomics 2013, 6, 39 .
AMA StyleEwa Szalowska, Geert Stoopen, Maria J Groot, Peter Jm Hendriksen, Ad Acm Peijnenburg. Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes. BMC Medical Genomics. 2013; 6 (1):39.
Chicago/Turabian StyleEwa Szalowska; Geert Stoopen; Maria J Groot; Peter Jm Hendriksen; Ad Acm Peijnenburg. 2013. "Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes." BMC Medical Genomics 6, no. 1: 39.
Ewa Szalowska; Geert Stoopen; Jeroen C.W. Rijk; Si Wang; Peter J.M. Hendriksen; Maria J. Groot; Jan Ossenkoppele; Ad A.C.M. Peijnenburg. Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices. Toxicology in Vitro 2013, 27, 1513 -1524.
AMA StyleEwa Szalowska, Geert Stoopen, Jeroen C.W. Rijk, Si Wang, Peter J.M. Hendriksen, Maria J. Groot, Jan Ossenkoppele, Ad A.C.M. Peijnenburg. Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices. Toxicology in Vitro. 2013; 27 (5):1513-1524.
Chicago/Turabian StyleEwa Szalowska; Geert Stoopen; Jeroen C.W. Rijk; Si Wang; Peter J.M. Hendriksen; Maria J. Groot; Jan Ossenkoppele; Ad A.C.M. Peijnenburg. 2013. "Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices." Toxicology in Vitro 27, no. 5: 1513-1524.