Respiratory Aflatoxicosis: Suppression of Pulmonary and Systemic Host Defenses in Rats and Mice

Jakab, George J.; Hmieleski, Robert R.; Zarba, Audrey; Hemenway, David R.; Groopman, John D.

doi:10.1006/taap.1994.1065

Cited by 90 publications

(44 citation statements)

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“…Jakab et al (1994) observed suppression of alveolar macrophage F c -receptor mediated phagocytosis following aerosol inhalation of AFB 1 in rats. Suppression of systemic immune function, as determined by splenic antibody response to sheep red blood cells and suppression of peritoneal macrophage phagocytosis, was observed with intratracheal instillation of AFB 1 at 10-fold higher doses compared to inhalation.…”

Section: Introductionmentioning

confidence: 85%

“…Assuming mice have the same percent alveolar deposition as rats (15%; Schlesinger, 1985), and a mouse body weight of 20 g, the highest dose level used in this study equates to an alveolar dose of 135 µg AFB 1 /kg. Jakab et al (1994) reported a local immunosuppressive effect of AFB 1 on alveolar macrophage phagocytosis in male Fischer 344 rats following inhalation exposure to 33.6 µg AFB 1 /kg BW, however other immune functions using this route of exposure were not examined. At an approximately four-fold higher dose (135 µg/kg BW), we observed no evidence of acute systemic AFB 1 immunotoxicity following inhalation exposure.…”

Section: Discussionmentioning

confidence: 99%

“…At an approximately four-fold higher dose (135 µg/kg BW), we observed no evidence of acute systemic AFB 1 immunotoxicity following inhalation exposure. It appears that for systemic immunosuppressive effects to occur a much higher dose, such as that delivered by intratracheal instillation (Jakab et al, 1994), or orally (Bondy and Pestka, 2000), would be required. The low solubility of AFB 1 in biologically compatible solvents limits achieving higher inhalation doses by nebulization of a solution.…”

Section: Discussionmentioning

confidence: 99%

“…Five studies with aerosol exposure to AF have been reported (Louria et al, 1974;Northrup et al, 1975;Richard et al, 1982;Zarba et al, 1992); however, only one study examined the immunotoxicity of AF (Jakab et al, 1994). Jakab et al (1994) observed suppression of alveolar macrophage F c -receptor mediated phagocytosis following aerosol inhalation of AFB 1 in rats.…”

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: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Los efectos tóxicos de las micotoxinas sobre la salud humana y animal son de curso crónico, incluyen carcinogenicidad, inmunosupresión y disrupciones endocrinas (4,5); la principal vía de exposición es la oral a través del consumo de alimentos contaminados, se presentan casos de micotoxicosis por inhalación (6)(7)(8).…”

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Micotoxinas en la Salud Pública

Duarte-Vogel¹,

Villamil-Jiménez²

2006

Rev. salud pública

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RESUMENLas micotoxinas constituyen un problema en el ámbito mundial por su alta incidencia y niveles de ocurrencia en los alimentos para humanos y animales. Las condiciones de colonización de los sustratos por hongos micotoxigénicos así como su posterior contaminación con micotoxinas juegan un papel fundamental en las estrategias de vigilancia y control. Entre los principales hongos micotoxigénicos se encuentran los géneros Aspergillus spp., Penicillium spp. y Fusarium spp. Dentro de las familias más importantes de micotoxinas se encuentran: las aflatoxinas, los tricoticenos, la ocratoxina A, las fumonisinas y la zearalenona. Los diferentes mecanismos de acción tóxica de estas micotoxinas constituyen un riesgo para la salud humana y animal constituyéndose en una problemática de salud pública. En Colombia la situación es compleja dada la deficiente investigación al respecto, los estudios realizados en el país han demostrado que la contaminación de alimentos por algunas micotoxinas es significativa y que se deben formular políticas sanitarias para afrontar este limitante. Se discute el riesgo potencial de las micotoxinas para la salud pública, las dificultades en el diagnóstico y la legislación así como las implicaciones en la seguridad e inocuidad alimentaria.Palabras Clave: Micotoxinas, salud pública, abastecimiento de alimentos, medicina veterinaria (fuente: DeCS, BIREME). ABSTRACT Micotoxins in Public HealthMycotoxins have become a worldwide problem due to their high incidence and levels of occurrence in human food and animal feed. The conditions for colonising substrates by mycotoxigenic fungus and later contamination by mycotoxins play an important role in surveillance and control strategies. The main mycotoxigenic funguses are the Aspergillus spp., Penicillium spp. and 129

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Effects of Stachybotrys chartarum atra conidia and isolated toxin on LungSurfactant production and homeostasis

et al. 1998

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This study evaluated the effects of Stachybotrys chartarum conidia and a trichothecene, isosatratoxin-F, on choline incorporation into DSPC by fetal rabbit alveolar type II cells and on alveolar surfactant subtypes in mice. Exposure of fetal rabbit type II cells to S. chartarum conidia at concentrations of 10(3) to 10(6) conidia ml(-1) significantly depressed [3H] choline incorporation after 24 h of exposure. Exposure of the rabbit cells to 10(5) to 10(6) conidia ml(-1) also resulted in significantly depressed [3H] choline uptake after 48 h. Additionally, fetal rabbit alveolar type II cells exposed to isosatratoxin-F in concentrations ranging from 10(-9) to 10(-4) M showed a significant reduction in [3H] choline incorporation into DSPC. Alveolar surfactant phospholipid concentrations in the different metabolic subfractions of lung lavage fluid of mice intratracheally exposed to either 50 microl of 10(7) ml(-1) S. chartarum conidia or 50 microl 10(-7) M isosatratoxin-F showed some significant changes at 12, 24, 48, and 72 h post-exposure, compared to the surfactant subfractions of control mice which were either untreated, exposed to saline or to 50 microl of 10(-7) ml(-1) Cladosporium cladosporioides conidia. In both the S. chartarum- and the isosatratoxin-F-treated mice, exposure significantly increased P10, P100, and S100 phospholipid concentrations, while the P60 phospholipid concentrations were depressed. In contrast, C. cladosporioides-treated mice showed only one significant change in subfraction phospholipid concentration: P60 was depressed at 48 h post-exposure. These results reveal that alveolar type II cells are sensitive to exposure to S. chartarum conidia and to isosatratoxin F. Sensitivity is manifest by alterations in the normal metabolic processing of alveolar surfactant. In exposed mice, this effect appears to involve a significant increase in newly secreted surfactant and an accumulation of the used surfactant forms.

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Respiratory Aflatoxicosis: Suppression of Pulmonary and Systemic Host Defenses in Rats and Mice

Cited by 90 publications

References 0 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

Micotoxinas en la Salud Pública

Effects of Stachybotrys chartarum atra conidia and isolated toxin on LungSurfactant production and homeostasis

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Respiratory Aflatoxicosis: Suppression of Pulmonary and Systemic Host Defenses in Rats and Mice

Cited by 90 publications

References 0 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

Micotoxinas en la Salud Pública

Effects of Stachybotrys chartarum atra conidia and isolated toxin on LungSurfactant production and homeostasis

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Product

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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