The effect of aflatoxin B1 on cytokine mrna and corresponding protein levels in peritoneal macrophages and splenic lymphocytes

Dugyala, Raviprakash R.; Sharma, Raghubir P.

doi:10.1016/s0192-0561(96)00066-5

Cited by 63 publications

(34 citation statements)

References 26 publications

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“…Consistent with our study, Dugyala and Sharma (1996) reported no effect of AFB 1 on liver, kidney, spleen and thymus weights, and red blood cell and white blood cell concentrations at oral doses up to 700 µg AFB 1 /kg BW administered every other day for 2 weeks to male CD-1 mice. This study also observed no significant effect of AFB 1 treatment on Con-A-induced production of IL-2, IFNγ , and IL-3 by splenic lymphocytes.…”

Section: Discussionsupporting

confidence: 92%

“…AF ingestion does not appear to alter immunoregulatory cytokine production (Dugyala and Sharma, 1996;Watzl et al, 1999;Marin et al, 2002) or the humoral response to sheep red blood cells (van Heugten et al, 1994) and Erysipelothrix rhusiopathiae (Panangala et al, 1986). Weanling pigs fed low doses of AF for 4 weeks, displayed no alterations in the relative numbers of blood cells, globulin, albumins, serum protein concentration, or phytohemagglutinin (PHA)-induced expression of IL-2 or IL-4 using whole blood, indicating that there was no effect of AF on the cell-mediated immune response (Marin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice

Sabourin

Price

Casbohm

et al. 2006

Journal of Immunotoxicology

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There is evidence for immunotoxicity of aflatoxin B1 (AFB 1 ) in chronic animal feeding studies; however, little information is available as to the effects of inhalation exposure. This study evaluated the acute affects of aerosolized AFB 1 on systemic immune function of female C57BL/6N mice following a single aerosol exposure. Mice were exposed in nose-only inhalation tubes to 0, 2.86, 6.59 and 10 µg AFB 1 aerosol/L air for 90 minutes. A negative control group of untreated mice and a positive control group of cyclophosphamide-treated mice were included to account for day to day variation. Three days following exposure, mice were sacrificed and body, liver, lung, thymus and spleen weights, and complete blood counts and white blood cell differentials were measured. Splenocytes were isolated for flow cytometric analysis of CD4 + and CD8 + lymphocytes, CD19 + B-cells and natural killer cells (NK 1.1 + ). The effect of AFB 1 on humoral immunity was assessed by measuring serum anti-keyhole limpet hemocyanin (KLH) IgM levels. Of the tissues examined, only the thymus weight of AFB 1 exposed mice decreased significantly compared to naïve mice; however, the decrease was not dose related and was also observed in the 0 AFB 1 aerosol control group. A decrease in the mean white blood cell count of treated vs. naïve mice was observed at all dose levels but was clearly not dose related and was statistically significant only in the 0 and 2.86 µg/L groups. Red blood cell and platelet counts and white blood cell differentials were not significantly affected by AFB 1 . The number of CD4 + (helper T-cells), CD8 + (cytotoxic T-cells) and CD19 + (B-cells) decreased in spleens of AFB 1 aerosol exposed mice compared to naïve mice; however, the decrease was not dose-related and was also observed in the 0 AFB 1 exposure group. Dose-related changes in the CD4 + /CD8 + T-lymphocyte ratios were not observed. The IgM response to KLH was not significantly different in AFB 1 compared to naïve mice, suggesting that AFB 1 did not effect antigen-specific antibody production. Based on the results of this study, a single AFB 1 inhalation exposure up to 10 µg/L for 90 minutes (CxT = 900 µg·min/L) did not significantly alter the immune parameters measured in this study. The aerosol vehicle (ethanol) and/or stress could have masked subtle AFB 1 -dependent changes in thymus and spleen weights, and in splenic lymphocyte subpopulations. However, for other immunological parameters, such as the IgM response

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice

Sabourin

Price

Casbohm

et al. 2006

Journal of Immunotoxicology

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“…AFB1 is known to initiate hepatic inflammation, and correspondingly, was shown to affect expression of pro-inflammatory cytokines in both mammals and poultry [124,171,[222][223][224][225][226]. Splenic expression of interleukins 1 beta (IL1β), 6 (IL6), 10 (IL10), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in pigs (Sus scrofa) were increased by AFB1 exposure [225].…”

Section: Cytokines and The Mhcmentioning

confidence: 99%

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

2015

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This review is a comprehensive introduction to the effects of poultry exposure to the toxic and carcinogenic mycotoxin aflatoxin B1 (AFB1). The relationship between AFB1 sensitivity and metabolism, major direct and indirect effects of AFB1, recent studies of gene expression and transcriptome responses to exposure, and mitigation strategies to reduce toxicity are discussed. Exposure to AFB1 primarily occurs by consumption of contaminated corn, grain or other feed components. Low levels of residual AFB1 in poultry feeds can cause reduction in growth, feed conversion, egg production, and compromised immune functions, resulting in significant economic costs to producers. Thus, AFB1 acts as a "force multiplier" synergizing the adverse effects of microbial pathogens and other agents, and factors detrimental to poultry health. Domestic turkeys (Meleagris gallopavo) are one of the most sensitive animals known to AFB1 due, in large part, to a combination of efficient hepatic bioactivation by cytochromes P450 1A5 and 3A37, and deficient hepatic glutathione-S-transferase (GST)-mediated detoxification. Because of their sensitivity, turkeys are a good model to investigate chemopreventive treatments and feed additives for their ability to reduce AFB1 toxicity. Transcriptome analysis (RNA-seq) of turkey poults (liver and spleen) has identified AFB1-induced gene expression changes in pathways of apoptosis, carcinogenesis, lipid regulation, antimicrobial activity, cytotoxicity and antigen presentation. Current research focuses on further identifying the molecular mechanisms OPEN ACCESSAgriculture 2015, 5 743 underlying AFB1 toxicity with the goal of reducing aflatoxicosis and improving poultry health.

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“…In Japan, there are permissible concentrations of the mycotoxins aflatoxin B 1 (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN) in feed for animals. There have been many studies on the effects of mycotoxins on the immune functions of various animals [1][2][3][4][5][6][7][8][9][10][11][12]15]. We previously conducted blood profile tests for cows on dairy farms that were given feed contaminated with mycotoxins (mainly AFB 1 ) and found reduced levels of T cells in many cows [14].…”

mentioning

confidence: 99%

“…Dugyala et al [6] and Hinton et al [7] showed using mice and rats that AFB 1 facilitates or suppresses PBMC proliferation according to dose and inoculation time. Thus, a low concentration of AFB 1 possibly stimulates PBMC proliferation.…”

mentioning

confidence: 99%

Effects of Mycotoxins on Mitogen-stimulated Proliferation of Bovine Peripheral Blood Mononuclear Cells

Wada¹,

Hashiba

Ohtsuka

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. The effects of mycotoxins on mitogen-stimulated proliferation of bovine peripheral blood mononuclear cells (PBMCs) were investigated. Aflatoxin B 1 (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN) were added to cultures of PBMCs, and the proliferation responses were measured using MTT bioassays. Suppression of the proliferation of calf PBMCs by AFB 1 and DON was significantly stronger than that of cow PBMCs, whereas there were no differences in suppressive effects on PBMCs from Holstein and Japanese Black calves and cows. The suppressive effect was greatest in the order of DON, AFB 1 and ZEN, and the effects of DON and AFB 1 seemed to be dose-dependent. The results suggest that some mycotoxins directly suppress proliferation of bovine PBMCs. KEY WORDS: bovine, mononuclear cell, mycotoxin.J. Vet. Med. Sci. 70(2): 193-196, 2008 Mycotoxin is a general term for harmful substances produced by certain fungi. In Japan, there are permissible concentrations of the mycotoxins aflatoxin B 1 (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN) in feed for animals. There have been many studies on the effects of mycotoxins on the immune functions of various animals [1][2][3][4][5][6][7][8][9][10][11][12]15]. We previously conducted blood profile tests for cows on dairy farms that were given feed contaminated with mycotoxins (mainly AFB 1 ) and found reduced levels of T cells in many cows [14]. These findings indicate that mycotoxins may induce immune suppression, particularly suppression of bovine T-lymphocyte function. However, the relationships between the direct effect of a mycotoxin on bovine peripheral blood mononuclear cells (PBMCs) and age or breed has not been elucidated. Moreover, there have been only a few studies in which the effects of various mycotoxins were examined [4,5]. The aim of this study was therefore to clarify the effects of AFB1, DON and ZEN on proliferation of bovine PBMCs.The cattle tested were clinically healthy Holstein cows (n=6), Japanese Black cows (n=6), Holstein calves (n=6, =1, =5) and Japanese Black calves (n=6, =3, =3). The cows were between 3 and 7 years old, and the calves were between 1 and 2 months old. Aflatoxin B 1 from Aspergillus flavus (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN; Sigma-Aldrich Co., St. Louis, MO, U.S.A.) were used as mycotoxin reagents.Blood was collected from each animal into sampling tubes containing heparin. Each 5 ml blood sample was diluted with 5 ml 1/15M PBS (pH #7.4) and laid on 4.5 ml Lymphocepar I (Immuno-Biological Laboratories Co., Ltd. Gunma, Japan). PBMCs were isolated by centrifugation (1,500 rpm, 60 min) and washed several times with PBS. The samples were seeded into 96-well microplates at 1 × 10 6 cells/well and diluted with 10% FCS-containing RPMI Medium 1640 (Gibco BRL, Gaithersburg, MD, U.S.A.) at a final volume of 200 µl/well. Ten µg/ml of phytohaemagglutin-P (PHA-P; Sigma-Aldrich Co.) was added to each PBMC culture, and then each culture was mixed with AFB 1 , DON, ZEN, AFB 1 +DON, AFB 1 +ZEN or DON+ZEN and incubated f...

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The effect of aflatoxin B1 on cytokine mrna and corresponding protein levels in peritoneal macrophages and splenic lymphocytes

Cited by 63 publications

References 26 publications

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Effects of Mycotoxins on Mitogen-stimulated Proliferation of Bovine Peripheral Blood Mononuclear Cells

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The effect of aflatoxin B1 on cytokine mrna and corresponding protein levels in peritoneal macrophages and splenic lymphocytes

Cited by 63 publications

References 26 publications

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B1in Female C57BL/6N Mice

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B1in Female C57BL/6N Mice

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Effects of Mycotoxins on Mitogen-stimulated Proliferation of Bovine Peripheral Blood Mononuclear Cells

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Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B₁in Female C57BL/6N Mice