Ionelia Taranu - Academia.edu (original) (raw)

Papers by Ionelia Taranu

Research paper thumbnail of JAS DM+IT (2002)

Research paper thumbnail of Microarray based gene expression analysis of Sus Scrofa duodenum exposed to zearalenone: significance to human health

BMC Genomics, 2016

Background: Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was pro... more Background: Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was proved to exert a wide range of unwanted side effects, but its mechanism of action, particularly at duodenum levels, remains unclear. In our study based on the microarray technology we assessed the alteration of gene expression pattern Sus scrofa duodenum which has been previously exposed to ZEA. Gene expression data was validated by qRT-PCR and ELISA. The gene expression data were further extrapolated the results to their human orthologues and analyzed the data in the context of human health using IPA (Ingenuity Pathways Analysis). Results: Using Agilent microarray technology, we found that gene expression pattern was significantly affected by ZEA exposure, considering a 2-fold expression difference as a cutoff level and a p-value < 0.05. In total, we found 1576 upregulated and 2446 downregulated transcripts. About 1084 genes (764 downregulated and 751 overexpressed) were extrapolated to their human orthologues. IPA analysis showed various altered key cellular and molecular pathways. As expected, we observed a significant alteration of immune response related genes, MAPK (mitogen activate protein kinases) pathways or Toll-Like Receptors (TLRs). What captured our attention was the modulation of pathways related to the activation of early carcinogenesis. Conclusions: Our data demonstrate that ZEA has a complex effect at duodenum level. ZEA is able to activate not only the immune response related genes, but also those relate to colorectal carcinogenesis. The effects can be more dramatic when connected with the exposure to other environmental toxic agents or co-occurrence with different microorganisms.

Research paper thumbnail of Immunotoxicology of mycotoxins produced by Fusarium fungi—Low concentrations of deoxynivalenol interfere with nucleotide metabolism

Research paper thumbnail of Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

The British journal of nutrition

Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a ri... more Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a risk factor from both public health and agricultural perspectives. In the present in vivo study, a feeding trial was conducted to evaluate the in vivo effect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β and interferon-γ) and anti-inflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARγ and NF-κB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38α)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant dec...

Research paper thumbnail of Zearalenone Mycotoxin Affects Immune Mediators, MAPK Signalling Molecules, Nuclear Receptors and Genome-Wide Gene Expression in Pig Spleen

PLOS ONE, 2015

The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and a... more The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and adaptative immune response. Weaned pigs were fed for 18 days with a control or a ZEA contaminated diet. The effect of ZEA was assessed on wide genome expression, pro-(TNFα, IL-8, IL-6, IL-1β, IFN-γ) and anti-inflammatory (IL-10, IL-4) cytokines, other molecules involved in inflammatory processes (MMPs/TIMPs), as well as signaling molecules, (p38/ JNK1/JNK2-MAPKs) and nuclear receptors (PPARγ/NFkB/AP-1/STAT3/c-JUN). Microarray analysis showed that 46% of total number of differentially expressed genes was involved in cellular signaling pathway, 13% in cytokine network and 10% in the inflammatory response. ZEA increased expression and synthesis of pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β) and had no effect on IFN-γ, IL-4 and IL-10 cytokines in spleen. The inflammatory stimulation might be a consequence of JNK pathway activation rather than of p-38MAPK and NF-kB involvement whose gene and protein expression were suppressed by ZEA action. In summary, our findings indicated the role of ZEA as an immune disruptor at spleen level.

Research paper thumbnail of Dietary ecologic camelina oil – a beneficial source of n-3 PUFA in muscle tissue and health status in finishing pigs

Postdoctoral School for zootechnical biodiversity and food biotechnology based on the eco-economy... more Postdoctoral School for zootechnical biodiversity and food biotechnology based on the eco-economy and the bio-economy required by eco-sanogenesis, ROMANIA. Abstract The objective of this study was to highlight the positive effects of the dietary ecologic camelina oil providing n-3 PUFA on fatty acid (FA) composition of total lipids of Longissimus dorsi, LD and Semitendinosus, ST muscles as well as its effects on blood plasma composition in finishing pigs. The experiment was carried for 30 days on 20 Large White finishing pigs randomly assigned to two isoenergetic and isonitrogenous diets: the control group (sunflower oil diet) received a diet including conventional ingredients based on sunflower oil (containing predominantly linoleic FA (C18:2n-6 = 64.62%) and the experimental group with supplement in n-3 PUFA by addition of camelina oil receiving a diet including ecological ingredients. Gas chromatography was used to determine the detailed composition in FA in muscle tissues (Longi...

Research paper thumbnail of Dietary zearalenone induces alteration in spleen inflammatory response by modulation of metalloproteinase, nuclear receptors and MAPKs gene expression

Annals of Nutrition and Metabolism

Research paper thumbnail of Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin

Journal of animal science, 2002

A feeding trial was conducted to evaluate the effect of aflatoxin (AF)-contaminated diets on grow... more A feeding trial was conducted to evaluate the effect of aflatoxin (AF)-contaminated diets on growth and hematological and immunological parameters. Low doses of aflatoxins (140 and 280 ppb) were included in a corn-soybean diet provided for ad libitum consumption to 36 weanling piglets for a period of 4 wk. A "dose-related" decrease in weight gain was observed in treated animals. This effect was significant (P < 0.05) in the 280 ppb-treated group compared to the control group. Ingestion of AF-contaminated feed at either level had no effect on total red blood cell numbers or on their relative number of lymphocytes, monocytes, neutrophils, basophils, and eosinophils in blood. Likewise, AF did not alter globulin, albumins, or total protein concentrations in serum, nor did AF alter the expression of regulatory cytokines produced by either Th1 (IL-2) or Th2 (IL-4) lymphocyte subsets in phytohemagglutinin-stimulated blood samples. By contrast, AF had a biphasic effect on total...

Research paper thumbnail of Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

Toxins, 2015

Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxyn... more Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

Research paper thumbnail of Induction of pro-inflammatory gene expression by Escherichia coli and mycotoxin zearalenone contamination and protection by a Lactobacillus mixture in porcine IPEC-1 cells

Toxicon, 2015

and sharing with colleagues.

Research paper thumbnail of Exposure to zearalenone mycotoxin alters in vitro porcine intestinal epithelial cells by differential gene expression

Toxicology Letters, 2015

The gut represents the main route of intoxication with mycotoxins. To evaluate the effect and the... more The gut represents the main route of intoxication with mycotoxins. To evaluate the effect and the underlying molecular changes that occurred when the intestine is exposed to zearalenone, a Fusarium sp mycotoxin, porcine epithelial cells (IPEC-1) were treated with 10μM of ZEA for 24h and analysed by microarray using Gene Spring GX v.11.5. Our results showed that 10μM of ZEA did not affect cell viability, but can increase the expression of toll like receptors (TLR1-10) and of certain cytokines involved in inflammation (TNF-α, IL-1β, IL-6, IL-8, MCP-1, IL-12p40, CCL20) or responsible for the recruitment of immune cells (IL-10, IL-18). Microarray results identified 190 genes significantly and differentially expressed, of which 70% were up-regulated. ZEA determined the over expression of ITGB5 gene, essential against the attachment and adhesion of ETEC to porcine jejunal cells and of TFF2 implicated in mucosal protection. An up-regulation of glutathione peroxidase enzymes (GPx6, GPx2, GPx1) was also observed. Upon ZEA challenge, genes like GTF3C4 responsible for the recruitment of polymerase III and initiation of tRNA transcription in eukaryotes and STAT5B were significantly higher induced. The up-regulation of CD97 gene and the down-regulation of tumour suppressor genes (DKK-1, PCDH11X and TC531386) demonstrates the carcinogenic potential of ZEA.

Research paper thumbnail of ω-3 PUFA Rich Camelina Oil By-Products Improve the Systemic Metabolism and Spleen Cell Functions in Fattening Pigs

PLoS ONE, 2014

Camelina oil-cakes results after the extraction of oil from Camelina sativa plant. In this study,... more Camelina oil-cakes results after the extraction of oil from Camelina sativa plant. In this study, camelina oil-cakes were fed to fattening pigs for 33 days and its effect on performance, plasma biochemical analytes, pro-/anti-inflammatory mediators and antioxidant detoxifying defence in spleen was investigated in comparison with sunflower meal. 24 crossbred TOPIG pigs were randomly assigned to one of two experimental dietary treatments containing either 12% sunflower meal (treatment 1-T1), or 12.0% camelina oil-cakes, rich in polyunsaturated fatty acids v-3 (v-3 PUFA) (treatment 2-T2). The results showed no effect of T2 diet (camelina cakes) on feed intake, average weight gain or feed efficiency. Consumption of camelina diet resulted in a significant decrease in plasma glucose concentration (18.47%) with a trend towards also a decrease of plasma cholesterol. In spleen, T2 diet modulated cellular immune response by decreasing the protein and gene expression of pro-inflammatory markers, interleukin 1-beta (IL-1b), tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6) and interleukin (IL-8) and cyclooxigenase 2 (COX-2) in comparison with T1 diet. By contrast, T2 diet increased (P,0.05) in spleen the mRNA expression of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase 1 (GPx1) by 3.43, 2.47 and 1.83 fold change respectively, inducible nitric oxide synthase (iNOS) (4.60 fold), endothelial nitric oxide synthase (eNOS) (3.23 fold) and the total antioxidant level (9.02%) in plasma. Camelina diet increased also peroxisome-proliferator activated receptor gamma (PPAR-c) mRNA and decreased that of mitogen-activated protein kinase 14 (p38a MAPK) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kB). At this level of inclusion (12%) camelina oil-cakes appears to be a potentially alternative feed source for pig which preserves a high content of v-3 PUFA indicating antioxidant properties by the stimulation of detoxifying enzymes expression and the suppression of spleen pro-inflammatory markers.

Research paper thumbnail of Current Situation of Mycotoxin Contamination and Co-occurrence in Animal Feed—Focus on Europe

Toxins, 2012

Mycotoxins are secondary metabolites produced by fungi especially those belonging to the genus As... more Mycotoxins are secondary metabolites produced by fungi especially those belonging to the genus Aspergillus, Penicillum and Fusarium. Mycotoxin contamination can occur in all agricultural commodities in the field and/or during storage, if conditions are favourable to fungal growth. Regarding animal feed, five mycotoxins (aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A) are covered by EU legislation (regulation or recommendation). Transgressions of these limits are rarely observed in official monitoring programs. However, low level contamination by Fusarium toxins is very common (e.g., deoxynivalenol (DON) is typically found in more than 50% of the samples) and co-contamination is frequently observed. Multi-mycotoxin studies reported 75%-100% of the samples to contain more than one mycotoxin which could impact animal

Research paper thumbnail of decreases the vaccinal antibody titer in pigs

1 2 Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed... more 1 2 Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed 3 and food. In the present study, we investigated the effect of FB 1 on the modulation of cytokine 4 profile and on the establishment of a vaccinal antibody response. In vitro investigations on pig 5 peripheral blood mononuclear cells (PBMC) indicate that FB 1 decreased IL-4 and increased IFN-6 synthesis at both the protein and mRNA levels. A short in vivo exposure (7 days) of weanling 7 piglets to 1.5 mg/kg body weight of purified FB 1 altered the cytokine balance in mesenteric 8 lymph nodes and spleen similarly to the in vitro PBMC results. We also investigated the effect of 9 FB 1 on the antibody response during a vaccination process. A prolonged in vivo exposure (28 10 days) of weaning piglets to feed contaminated with 8 mg FB 1 /Kg significantly decreased the 11 expression of IL-4 mRNA by porcine whole blood cells and diminished the specific antibody titer 12 after vaccination against Mycoplasma agalactiae. By contrast, ingestion of the contaminated feed 13 had no effect on the serum concentration of the immunoglobulin subset (IgG, IgA and IgM). 14 Taken together our data suggest that, FB 1 alters the cytokine profile and decrease the specific 15 antibody response build during a vaccination protocol. These results may have implications for 16 human or animals when eating contaminated food or feed. 17 18

Research paper thumbnail of Overview on aflatoxins and oxidative stress

Research paper thumbnail of Effects of zearalenone and its derivatives on the innate immune response of swine

Toxicon, 2010

Swine Immunity a b s t r a c t Zearalenone (ZEN) is an estrogenic mycotoxin produced by several f... more Swine Immunity a b s t r a c t Zearalenone (ZEN) is an estrogenic mycotoxin produced by several fungi of Fusarium genera. As it can contaminate food and feed it is a risk factor from both public health and agricultural perspectives. In this in vitro study, we compared the effects of zearalenone (ZEN) and some of its derivatives: a-zearalenol (a-ZOL); b-zearalenol (b-ZOL) and zearalanone (ZAN) on several neutrophil functions: proliferation, cytokine synthesis and oxidative stress in a porcine PMN model. The concentrations of toxins necessary to inhibit viability, in a MTT test, by 50% were: 73.4 mM for ZEN; 59.0 mM for a-ZOL; 56.8 mM for b-ZOL and 53.1 mM for ZAN, with ZEN being less toxic than its derivatives. A significant increase of O 2 À synthesis compared to the control, as shown by NBT reduction, was observed at 1 mM concentration only for b-ZOL and ZAN, while at 10 mM, the ZEN derivatives (a-ZOL, b-ZOL, ZAN) induced a significant decrease of the IL-8 synthesis in swine PMNs with 49.2%, 45.6% and 45.1% respectively, compared to the control. Although, the precise mechanism of action of these toxins still remains unknown, the results of this study suggest that ZEN and its derivatives may have divergent effects on important parameters of swine innate immunity: cell proliferation, IL-8 and O 2 À synthesis. Also ZEN derivatives are more toxic than ZEN.

Research paper thumbnail of Immunotoxicology of mycotoxins produced by Fusarium fungi—Low concentrations of deoxynivalenol interfere with nucleotide metabolism

Research paper thumbnail of Evaluate the potential of a boron-fructose prebiotic (FructoB) in counteracting the toxic effect of Fusarium toxins

Research paper thumbnail of Effects of zearalenone and its derivatives on porcine immune response

Toxicology in Vitro, 2011

a-Zearalenol b-Zearalenol Zearalanone Swine PBMC Immunity a b s t r a c t Zearalenone (ZEN), a my... more a-Zearalenol b-Zearalenol Zearalanone Swine PBMC Immunity a b s t r a c t Zearalenone (ZEN), a mycotoxin produced by several Fusarium spp., is most commonly found as a contaminant in stored grain and has chronic estrogenic effects on mammals. In this in vitro study, we compared the effects of zearalenone (ZEN) and some of its derivatives: a-zearalenol (a-ZOL), b-zearalenol (b-ZOL), and zearalanone (ZAN) on several peripheral blood mononuclear cell (PBMC) parameters: cytotoxicity, proliferation, as well as antibody and cytokine synthesis. The amounts of toxins necessary to inhibit viability, in a dehydrogenase enzyme activity assay (MTT test), by 50% were: 22.7 lM for ZEN, 29.1 lM for a-ZOL, 17.3 lM for b-ZOL and 26.3 lM for ZAN. The administration of 10 lM toxin induced a decrease in the ConA stimulated proliferation of PBMC by 19.6% for ZAN, 45.4% for ZEN, 43.6% for a-ZOL and 85.2% for b-ZOL, when compared to the control stimulated cells. Also, ZEN and its metabolites at concentrations higher than 5 lM induced a significant decrease of the IgG, IgA or IgM levels. Concentrations of 5 and 10 lM of ZEN and ZAN significantly decreased the TNF-a synthesis in the supernatant of the stimulated cells; 10 lM of ZAN also decreased IL-8 synthesis. In conclusion, our results show that ZEN and ZEN derivatives altered several parameters of the humoral and cellular immune response.

Research paper thumbnail of Mycotoxin Fumonisin B1 Alters the Cytokine Profile and Decreases the Vaccinal Antibody Titer in Pigs

Toxicological Sciences, 2005

Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed and... more Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed and food. In the present study, we investigated the effect of FB 1 on the modulation of the cytokine profile and on the establishment of a vaccinal antibody response. In vitro investigations on pig peripheral blood mononuclear cells (PBMC) indicate that FB 1 decreased interleukin-4 (IL-4) and increased interferon-gamma (IFN-g) synthesis at both the protein and mRNA levels. A short in vivo exposure (7 days) of weanling piglets to 1.5 mg/kg body weight of purified FB 1 altered the cytokine balance in mesenteric lymph nodes and spleen similarly to the in vitro PBMC results. We also investigated the effect of FB 1 on the antibody response during a vaccination process. A prolonged in vivo exposure (28 days) of weanling piglets to feed contaminated with 8 mg FB 1 /kg significantly decreased the expression of IL-4 mRNA by porcine whole blood cells and diminished the specific antibody titer after vaccination against Mycoplasma agalactiae. By contrast, ingestion of the contaminated feed had no effect on the serum concentration of the immunoglobulin subset (IgG, IgA, and IgM). Taken together, our data suggest that FB 1 alters the cytokine profile and decreases the specific antibody response built during a vaccination protocol. These results may have implications for humans or animals eating contaminated food or feed.

Research paper thumbnail of JAS DM+IT (2002)

Research paper thumbnail of Microarray based gene expression analysis of Sus Scrofa duodenum exposed to zearalenone: significance to human health

BMC Genomics, 2016

Background: Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was pro... more Background: Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was proved to exert a wide range of unwanted side effects, but its mechanism of action, particularly at duodenum levels, remains unclear. In our study based on the microarray technology we assessed the alteration of gene expression pattern Sus scrofa duodenum which has been previously exposed to ZEA. Gene expression data was validated by qRT-PCR and ELISA. The gene expression data were further extrapolated the results to their human orthologues and analyzed the data in the context of human health using IPA (Ingenuity Pathways Analysis). Results: Using Agilent microarray technology, we found that gene expression pattern was significantly affected by ZEA exposure, considering a 2-fold expression difference as a cutoff level and a p-value < 0.05. In total, we found 1576 upregulated and 2446 downregulated transcripts. About 1084 genes (764 downregulated and 751 overexpressed) were extrapolated to their human orthologues. IPA analysis showed various altered key cellular and molecular pathways. As expected, we observed a significant alteration of immune response related genes, MAPK (mitogen activate protein kinases) pathways or Toll-Like Receptors (TLRs). What captured our attention was the modulation of pathways related to the activation of early carcinogenesis. Conclusions: Our data demonstrate that ZEA has a complex effect at duodenum level. ZEA is able to activate not only the immune response related genes, but also those relate to colorectal carcinogenesis. The effects can be more dramatic when connected with the exposure to other environmental toxic agents or co-occurrence with different microorganisms.

Research paper thumbnail of Immunotoxicology of mycotoxins produced by Fusarium fungi—Low concentrations of deoxynivalenol interfere with nucleotide metabolism

Research paper thumbnail of Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

The British journal of nutrition

Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a ri... more Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a risk factor from both public health and agricultural perspectives. In the present in vivo study, a feeding trial was conducted to evaluate the in vivo effect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β and interferon-γ) and anti-inflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARγ and NF-κB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38α)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant dec...

Research paper thumbnail of Zearalenone Mycotoxin Affects Immune Mediators, MAPK Signalling Molecules, Nuclear Receptors and Genome-Wide Gene Expression in Pig Spleen

PLOS ONE, 2015

The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and a... more The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and adaptative immune response. Weaned pigs were fed for 18 days with a control or a ZEA contaminated diet. The effect of ZEA was assessed on wide genome expression, pro-(TNFα, IL-8, IL-6, IL-1β, IFN-γ) and anti-inflammatory (IL-10, IL-4) cytokines, other molecules involved in inflammatory processes (MMPs/TIMPs), as well as signaling molecules, (p38/ JNK1/JNK2-MAPKs) and nuclear receptors (PPARγ/NFkB/AP-1/STAT3/c-JUN). Microarray analysis showed that 46% of total number of differentially expressed genes was involved in cellular signaling pathway, 13% in cytokine network and 10% in the inflammatory response. ZEA increased expression and synthesis of pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β) and had no effect on IFN-γ, IL-4 and IL-10 cytokines in spleen. The inflammatory stimulation might be a consequence of JNK pathway activation rather than of p-38MAPK and NF-kB involvement whose gene and protein expression were suppressed by ZEA action. In summary, our findings indicated the role of ZEA as an immune disruptor at spleen level.

Research paper thumbnail of Dietary ecologic camelina oil – a beneficial source of n-3 PUFA in muscle tissue and health status in finishing pigs

Postdoctoral School for zootechnical biodiversity and food biotechnology based on the eco-economy... more Postdoctoral School for zootechnical biodiversity and food biotechnology based on the eco-economy and the bio-economy required by eco-sanogenesis, ROMANIA. Abstract The objective of this study was to highlight the positive effects of the dietary ecologic camelina oil providing n-3 PUFA on fatty acid (FA) composition of total lipids of Longissimus dorsi, LD and Semitendinosus, ST muscles as well as its effects on blood plasma composition in finishing pigs. The experiment was carried for 30 days on 20 Large White finishing pigs randomly assigned to two isoenergetic and isonitrogenous diets: the control group (sunflower oil diet) received a diet including conventional ingredients based on sunflower oil (containing predominantly linoleic FA (C18:2n-6 = 64.62%) and the experimental group with supplement in n-3 PUFA by addition of camelina oil receiving a diet including ecological ingredients. Gas chromatography was used to determine the detailed composition in FA in muscle tissues (Longi...

Research paper thumbnail of Dietary zearalenone induces alteration in spleen inflammatory response by modulation of metalloproteinase, nuclear receptors and MAPKs gene expression

Annals of Nutrition and Metabolism

Research paper thumbnail of Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin

Journal of animal science, 2002

A feeding trial was conducted to evaluate the effect of aflatoxin (AF)-contaminated diets on grow... more A feeding trial was conducted to evaluate the effect of aflatoxin (AF)-contaminated diets on growth and hematological and immunological parameters. Low doses of aflatoxins (140 and 280 ppb) were included in a corn-soybean diet provided for ad libitum consumption to 36 weanling piglets for a period of 4 wk. A "dose-related" decrease in weight gain was observed in treated animals. This effect was significant (P < 0.05) in the 280 ppb-treated group compared to the control group. Ingestion of AF-contaminated feed at either level had no effect on total red blood cell numbers or on their relative number of lymphocytes, monocytes, neutrophils, basophils, and eosinophils in blood. Likewise, AF did not alter globulin, albumins, or total protein concentrations in serum, nor did AF alter the expression of regulatory cytokines produced by either Th1 (IL-2) or Th2 (IL-4) lymphocyte subsets in phytohemagglutinin-stimulated blood samples. By contrast, AF had a biphasic effect on total...

Research paper thumbnail of Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

Toxins, 2015

Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxyn... more Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

Research paper thumbnail of Induction of pro-inflammatory gene expression by Escherichia coli and mycotoxin zearalenone contamination and protection by a Lactobacillus mixture in porcine IPEC-1 cells

Toxicon, 2015

and sharing with colleagues.

Research paper thumbnail of Exposure to zearalenone mycotoxin alters in vitro porcine intestinal epithelial cells by differential gene expression

Toxicology Letters, 2015

The gut represents the main route of intoxication with mycotoxins. To evaluate the effect and the... more The gut represents the main route of intoxication with mycotoxins. To evaluate the effect and the underlying molecular changes that occurred when the intestine is exposed to zearalenone, a Fusarium sp mycotoxin, porcine epithelial cells (IPEC-1) were treated with 10μM of ZEA for 24h and analysed by microarray using Gene Spring GX v.11.5. Our results showed that 10μM of ZEA did not affect cell viability, but can increase the expression of toll like receptors (TLR1-10) and of certain cytokines involved in inflammation (TNF-α, IL-1β, IL-6, IL-8, MCP-1, IL-12p40, CCL20) or responsible for the recruitment of immune cells (IL-10, IL-18). Microarray results identified 190 genes significantly and differentially expressed, of which 70% were up-regulated. ZEA determined the over expression of ITGB5 gene, essential against the attachment and adhesion of ETEC to porcine jejunal cells and of TFF2 implicated in mucosal protection. An up-regulation of glutathione peroxidase enzymes (GPx6, GPx2, GPx1) was also observed. Upon ZEA challenge, genes like GTF3C4 responsible for the recruitment of polymerase III and initiation of tRNA transcription in eukaryotes and STAT5B were significantly higher induced. The up-regulation of CD97 gene and the down-regulation of tumour suppressor genes (DKK-1, PCDH11X and TC531386) demonstrates the carcinogenic potential of ZEA.

Research paper thumbnail of ω-3 PUFA Rich Camelina Oil By-Products Improve the Systemic Metabolism and Spleen Cell Functions in Fattening Pigs

PLoS ONE, 2014

Camelina oil-cakes results after the extraction of oil from Camelina sativa plant. In this study,... more Camelina oil-cakes results after the extraction of oil from Camelina sativa plant. In this study, camelina oil-cakes were fed to fattening pigs for 33 days and its effect on performance, plasma biochemical analytes, pro-/anti-inflammatory mediators and antioxidant detoxifying defence in spleen was investigated in comparison with sunflower meal. 24 crossbred TOPIG pigs were randomly assigned to one of two experimental dietary treatments containing either 12% sunflower meal (treatment 1-T1), or 12.0% camelina oil-cakes, rich in polyunsaturated fatty acids v-3 (v-3 PUFA) (treatment 2-T2). The results showed no effect of T2 diet (camelina cakes) on feed intake, average weight gain or feed efficiency. Consumption of camelina diet resulted in a significant decrease in plasma glucose concentration (18.47%) with a trend towards also a decrease of plasma cholesterol. In spleen, T2 diet modulated cellular immune response by decreasing the protein and gene expression of pro-inflammatory markers, interleukin 1-beta (IL-1b), tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6) and interleukin (IL-8) and cyclooxigenase 2 (COX-2) in comparison with T1 diet. By contrast, T2 diet increased (P,0.05) in spleen the mRNA expression of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase 1 (GPx1) by 3.43, 2.47 and 1.83 fold change respectively, inducible nitric oxide synthase (iNOS) (4.60 fold), endothelial nitric oxide synthase (eNOS) (3.23 fold) and the total antioxidant level (9.02%) in plasma. Camelina diet increased also peroxisome-proliferator activated receptor gamma (PPAR-c) mRNA and decreased that of mitogen-activated protein kinase 14 (p38a MAPK) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kB). At this level of inclusion (12%) camelina oil-cakes appears to be a potentially alternative feed source for pig which preserves a high content of v-3 PUFA indicating antioxidant properties by the stimulation of detoxifying enzymes expression and the suppression of spleen pro-inflammatory markers.

Research paper thumbnail of Current Situation of Mycotoxin Contamination and Co-occurrence in Animal Feed—Focus on Europe

Toxins, 2012

Mycotoxins are secondary metabolites produced by fungi especially those belonging to the genus As... more Mycotoxins are secondary metabolites produced by fungi especially those belonging to the genus Aspergillus, Penicillum and Fusarium. Mycotoxin contamination can occur in all agricultural commodities in the field and/or during storage, if conditions are favourable to fungal growth. Regarding animal feed, five mycotoxins (aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A) are covered by EU legislation (regulation or recommendation). Transgressions of these limits are rarely observed in official monitoring programs. However, low level contamination by Fusarium toxins is very common (e.g., deoxynivalenol (DON) is typically found in more than 50% of the samples) and co-contamination is frequently observed. Multi-mycotoxin studies reported 75%-100% of the samples to contain more than one mycotoxin which could impact animal

Research paper thumbnail of decreases the vaccinal antibody titer in pigs

1 2 Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed... more 1 2 Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed 3 and food. In the present study, we investigated the effect of FB 1 on the modulation of cytokine 4 profile and on the establishment of a vaccinal antibody response. In vitro investigations on pig 5 peripheral blood mononuclear cells (PBMC) indicate that FB 1 decreased IL-4 and increased IFN-6 synthesis at both the protein and mRNA levels. A short in vivo exposure (7 days) of weanling 7 piglets to 1.5 mg/kg body weight of purified FB 1 altered the cytokine balance in mesenteric 8 lymph nodes and spleen similarly to the in vitro PBMC results. We also investigated the effect of 9 FB 1 on the antibody response during a vaccination process. A prolonged in vivo exposure (28 10 days) of weaning piglets to feed contaminated with 8 mg FB 1 /Kg significantly decreased the 11 expression of IL-4 mRNA by porcine whole blood cells and diminished the specific antibody titer 12 after vaccination against Mycoplasma agalactiae. By contrast, ingestion of the contaminated feed 13 had no effect on the serum concentration of the immunoglobulin subset (IgG, IgA and IgM). 14 Taken together our data suggest that, FB 1 alters the cytokine profile and decrease the specific 15 antibody response build during a vaccination protocol. These results may have implications for 16 human or animals when eating contaminated food or feed. 17 18

Research paper thumbnail of Overview on aflatoxins and oxidative stress

Research paper thumbnail of Effects of zearalenone and its derivatives on the innate immune response of swine

Toxicon, 2010

Swine Immunity a b s t r a c t Zearalenone (ZEN) is an estrogenic mycotoxin produced by several f... more Swine Immunity a b s t r a c t Zearalenone (ZEN) is an estrogenic mycotoxin produced by several fungi of Fusarium genera. As it can contaminate food and feed it is a risk factor from both public health and agricultural perspectives. In this in vitro study, we compared the effects of zearalenone (ZEN) and some of its derivatives: a-zearalenol (a-ZOL); b-zearalenol (b-ZOL) and zearalanone (ZAN) on several neutrophil functions: proliferation, cytokine synthesis and oxidative stress in a porcine PMN model. The concentrations of toxins necessary to inhibit viability, in a MTT test, by 50% were: 73.4 mM for ZEN; 59.0 mM for a-ZOL; 56.8 mM for b-ZOL and 53.1 mM for ZAN, with ZEN being less toxic than its derivatives. A significant increase of O 2 À synthesis compared to the control, as shown by NBT reduction, was observed at 1 mM concentration only for b-ZOL and ZAN, while at 10 mM, the ZEN derivatives (a-ZOL, b-ZOL, ZAN) induced a significant decrease of the IL-8 synthesis in swine PMNs with 49.2%, 45.6% and 45.1% respectively, compared to the control. Although, the precise mechanism of action of these toxins still remains unknown, the results of this study suggest that ZEN and its derivatives may have divergent effects on important parameters of swine innate immunity: cell proliferation, IL-8 and O 2 À synthesis. Also ZEN derivatives are more toxic than ZEN.

Research paper thumbnail of Immunotoxicology of mycotoxins produced by Fusarium fungi—Low concentrations of deoxynivalenol interfere with nucleotide metabolism

Research paper thumbnail of Evaluate the potential of a boron-fructose prebiotic (FructoB) in counteracting the toxic effect of Fusarium toxins

Research paper thumbnail of Effects of zearalenone and its derivatives on porcine immune response

Toxicology in Vitro, 2011

a-Zearalenol b-Zearalenol Zearalanone Swine PBMC Immunity a b s t r a c t Zearalenone (ZEN), a my... more a-Zearalenol b-Zearalenol Zearalanone Swine PBMC Immunity a b s t r a c t Zearalenone (ZEN), a mycotoxin produced by several Fusarium spp., is most commonly found as a contaminant in stored grain and has chronic estrogenic effects on mammals. In this in vitro study, we compared the effects of zearalenone (ZEN) and some of its derivatives: a-zearalenol (a-ZOL), b-zearalenol (b-ZOL), and zearalanone (ZAN) on several peripheral blood mononuclear cell (PBMC) parameters: cytotoxicity, proliferation, as well as antibody and cytokine synthesis. The amounts of toxins necessary to inhibit viability, in a dehydrogenase enzyme activity assay (MTT test), by 50% were: 22.7 lM for ZEN, 29.1 lM for a-ZOL, 17.3 lM for b-ZOL and 26.3 lM for ZAN. The administration of 10 lM toxin induced a decrease in the ConA stimulated proliferation of PBMC by 19.6% for ZAN, 45.4% for ZEN, 43.6% for a-ZOL and 85.2% for b-ZOL, when compared to the control stimulated cells. Also, ZEN and its metabolites at concentrations higher than 5 lM induced a significant decrease of the IgG, IgA or IgM levels. Concentrations of 5 and 10 lM of ZEN and ZAN significantly decreased the TNF-a synthesis in the supernatant of the stimulated cells; 10 lM of ZAN also decreased IL-8 synthesis. In conclusion, our results show that ZEN and ZEN derivatives altered several parameters of the humoral and cellular immune response.

Research paper thumbnail of Mycotoxin Fumonisin B1 Alters the Cytokine Profile and Decreases the Vaccinal Antibody Titer in Pigs

Toxicological Sciences, 2005

Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed and... more Fumonisin B 1 (FB 1 ), a mycotoxin produced by Fusarium verticillioides, may contaminate feed and food. In the present study, we investigated the effect of FB 1 on the modulation of the cytokine profile and on the establishment of a vaccinal antibody response. In vitro investigations on pig peripheral blood mononuclear cells (PBMC) indicate that FB 1 decreased interleukin-4 (IL-4) and increased interferon-gamma (IFN-g) synthesis at both the protein and mRNA levels. A short in vivo exposure (7 days) of weanling piglets to 1.5 mg/kg body weight of purified FB 1 altered the cytokine balance in mesenteric lymph nodes and spleen similarly to the in vitro PBMC results. We also investigated the effect of FB 1 on the antibody response during a vaccination process. A prolonged in vivo exposure (28 days) of weanling piglets to feed contaminated with 8 mg FB 1 /kg significantly decreased the expression of IL-4 mRNA by porcine whole blood cells and diminished the specific antibody titer after vaccination against Mycoplasma agalactiae. By contrast, ingestion of the contaminated feed had no effect on the serum concentration of the immunoglobulin subset (IgG, IgA, and IgM). Taken together, our data suggest that FB 1 alters the cytokine profile and decreases the specific antibody response built during a vaccination protocol. These results may have implications for humans or animals eating contaminated food or feed.