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1.
Environ Pollut ; 222: 154-164, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28089466

RESUMEN

A broad suite of 87 contaminants of emerging concern (CECs), including 26 polybrominated diphenyl ethers (PBDEs), 23 non-PBDEs halogenated FRs (NPHFRs), 16 organophosphate esters (OPEs), 4 perfluorinated sulfonates (PFSAs), 13 perfluorinated carboxylic acids (PFCAs) and 5 emerging perfluoroalkyl acids (PFAAs) or precursors, were determined in 30 individual Caspian tern (listed as a threatened species in the U.S. State of Michigan) eggs collected in 2013 and 2014 from Michigan nesting sites on Two Tree Island (St, Mary's River), Charity Reef (Saginaw Bay) and Channel-Shelter Island (a Confined Disposal Facility (CDF) in Saginaw Bay). The same CEC suite was determined in 10 herring gull eggs on the Pipe Island Twins in the lower St. Mary's River. In tern eggs, the order of concentrations were ΣPFSA (mean: 793 ng/g wet weight (ww); range: 116-4690 ng/g ww) > ΣPFCAs (131; 30.4-506 ng/g ww) ≈ ΣPBDEs (86.7; 32.4-189 ng/g ww) ¼ ΣNPHFRs (0.67; ND-4.3 ng/g ww) ≈ ΣOPEs (0.46; ND-2.89 ng/g ww). Compared to gull eggs collected from the same area, tern egg exposure contained significantly lower concentrations of ΣPBDE, but with up to 10 times greater mean concentrations of ΣPFSAs and ΣPFCAs. This study highlights the importance of consistent monitoring in eggs of different Great Lakes birds of PBDEs, perfluorooctane sulfonate (PFOS) and perfluoro-4-ethylcyclohexane sulfonate (PFEtCHxS) given that: 1) PBDE concentrations in all analyzed avian eggs exceeded or approached a concentration of 29 ng/g ww, which for birds is the current Canadian FEQG (Federal Environmental Quality Guideline); 2) ΣPBDE concentrations were comparable to lowest observed effect concentration (LOEC) values reported in the literature; 3) PFOS concentrations in Caspian tern eggs were extremely high with many eggs across sites exceeding 1 ppm, and with the greatest being up to 4.7 ppm; and 4) PFEtCHxS, a potentially persistent and bioaccumulative substance, showed a detection frequency of 100% in 40 of the analyzed eggs.


Asunto(s)
Charadriiformes/metabolismo , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Óvulo/química , Ácidos Alcanesulfónicos/análisis , Animales , Cruzamiento , Retardadores de Llama/análisis , Fluorocarburos/análisis , Éteres Difenilos Halogenados/análisis , Michigan
2.
Environ Toxicol Chem ; 32(3): 548-61, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23212976

RESUMEN

Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs. The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003. In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively). The phytohemagglutinin (PHA) skin response assessed T cell function in gull and heron chicks. Lymphocyte proliferation was measured in vitro in adult and prefledgling gulls. Reference data came from the Great Lakes and Bay of Fundy. Survival of prefledgling gulls was poor, with only 0.68 and 0.5 chicks per nest surviving to three and four weeks after hatch, respectively. Developing lymphoid cells were reduced 51% in the thymus and 42% in the bursa of gull embryos from New York Harbor. In vitro lymphocyte assays demonstrated reduced spontaneous proliferation, reduced T cell mitogen-induced proliferation, and increased B cell mitogen-induced proliferation in gull chicks from New York Harbor. The PHA skin response was suppressed 70 to 80% in gull and heron chicks. Strong negative correlations (r = -0.95 to -0.98) between the PHA response and dioxins and PCBs in gull livers was strong evidence suggesting that these chemicals contribute significantly to immunosuppression in New York Harbor waterbirds.


Asunto(s)
Aves/fisiología , Hidrocarburos Clorados/metabolismo , Metales/metabolismo , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/metabolismo , Animales , Aves/inmunología , Charadriiformes/inmunología , Charadriiformes/fisiología , Monitoreo del Ambiente , Estuarios , Hidrocarburos Clorados/toxicidad , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/fisiología , Metales/toxicidad , New York , Óvulo/metabolismo , Salud Reproductiva/estadística & datos numéricos , Contaminantes Químicos del Agua/toxicidad
3.
Environ Toxicol Chem ; 31(10): 2399-407, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22865698

RESUMEN

The current understanding of methylmercury (MeHg) toxicity to avian species has improved considerably in recent years and indicates that exposure to environmentally relevant concentrations of MeHg through the diet can adversely affect various aspects of avian health, reproduction, and survival. Because fish-eating birds are at particular risk for elevated MeHg exposure, the authors surveyed the available primary and secondary literature to summarize the effects of dietary MeHg on the common loon (Gavia immer) and to derive ecologically relevant toxic thresholds for dietary exposure to MeHg in fish prey. After considering the available data, the authors propose three screening benchmarks of 0.1, 0.18, and 0.4 µg g(-1) wet weight MeHg in prey fish. The lowest benchmark (0.1 µg g(-1) wet wt) is the threshold for adverse behavioral impacts in adult loons and is close to the empirically determined no observed adverse effects level for subclinical effects observed in captive loon chicks. The remaining benchmarks (0.18 and 0.4 µg g(-1) wet wt) correspond to MeHg levels in prey fish associated with significant reproductive impairment and reproductive failure in wild adult loons. Overall, these benchmarks incorporate recent findings and reviews of MeHg toxicity in aquatic fish-eating birds and provide the basis for a national ecological risk assessment for Hg and loons in Canada.


Asunto(s)
Aves/fisiología , Monitoreo del Ambiente , Cadena Alimentaria , Compuestos de Metilmercurio/toxicidad , Reproducción , Animales , Conducta Animal , Canadá , Dieta , Ecotoxicología , Determinación de Punto Final , Peces , Medición de Riesgo
4.
Methods Mol Biol ; 598: 387-98, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19967526

RESUMEN

Various methods have been adapted for assessing the effects of environmental contaminants on the structure and function of the immune system in wild and captive birds. This chapter describes two integrative functional assays that have been adapted to a variety of avian species and have proven to be sensitive biomarkers for immunotoxicological effects. The phytohemagglutinin (PHA) skin test measures T cell-mediated immunity. PHA is injected intra- or sub-dermally into the wing web of the elbow joint (or interdigitary skin or wattle). The PHA stimulates T lymphocytes to release cytokines that cause an inflammatory influx of leukocytes and fluid. The thickness of the wing web is measured before and 24 h after injection. A stimulation index, which reflects T cell function, is calculated as the increase in skin thickness caused by the PHA minus the increase caused by an injection of phosphate buffered saline (PBS) in the other wing web. In addition to its sensitivity to contaminants, ecological studies have shown that the PHA skin response is positively associated with rates of survival and colonization of new areas (i.e., ability to found new local populations) in wild birds.The sheep red blood cell (SRBC) hemagglutination assay measures the antibody response to immunization with SRBC antigens, integrating the functions of B lymphocytes, helper T lymphocytes, and macrophages. A SRBC suspension is injected i.v., and a blood sample is collected approximately 6 days later. Plasma (or serum) from the blood sample is serially diluted in a microtiter plate, and SRBCs are added. The magnitude of the antibody response is defined as the titer - the highest dilution of plasma in which the concentration of antibody is sufficient to agglutinate the SRBCs. Both IgM and IgG titers can be measured. This avian test is very similar in principle to the anti-SRBC ELISA and splenic plaque forming assays used for immunotoxicological testing in rodents. However, this avian hemagglutination assay does not require a species-specific secondary antibody (as does the ELISA), and this minimally invasive, nonlethal procedure is amenable to studies of protected species, as opposed to the splenic assay. The PHA and SRBC assays have been employed successfully in both the laboratory and field. In ecological studies birds must be recaptured 24 h or 6 days after the initial injections, limiting their use in some species. However, their sensitivity to a variety of contaminants and their ease of adaptability to a variety of species have made the PHA and SRBC tests some of the most commonly used assays for screening and monitoring immunotoxicity in birds.


Asunto(s)
Aves/inmunología , Contaminantes Ambientales/toxicidad , Pruebas de Hemaglutinación/métodos , Sistema Inmunológico/efectos de los fármacos , Pruebas de Toxicidad/métodos , Animales , Biomarcadores/metabolismo , Eritrocitos/inmunología , Sistema Inmunológico/fisiología , Inmunidad Celular/inmunología , Fitohemaglutininas/inmunología , Ovinos , Linfocitos T/inmunología
5.
J Toxicol Environ Health A ; 70(17): 1443-70, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17687730

RESUMEN

Tissues of 156 adult herring gulls (Larus argentatus) were sampled in the early 1990s from 11 colonies throughout the Laurentian Great Lakes and 2 reference colonies in Lake Winnipeg and the Bay of Fundy. Gulls from 1 or more Great Lakes differed from Lake Winnipeg or the Bay of Fundy for 17 of 19 clinical biochemical measures, whereas the freshwater and marine reference sites differed in only 3. Three differed with sex. There was little evidence to suggest that these differences reflect genotypic differences. Plasma thyroxine, albumin, calcium, magnesium, inorganic phosphorus, triglyceride, bile acids, total protein, uric acid, and urea nitrogen concentrations and aspartate aminotransferase (AST) activity were lower in gulls from one or more Great Lakes than for gulls from one or both reference sites, while those for globulins and glucose were higher. Highly carboxylated porphyrins accumulated in the livers of Great Lakes gulls and ethoxyresorufin O-deethylase (EROD) activity was induced. There was resistance to PCB/TCDD-induced EROD induction in the Lake Erie colonies. Gulls from five colonies were unable to obtain adequate food to maintain average body condition. Body condition was associated with seven biochemical measures. Colonies in designated Areas of Concern as well as those with high liver polychlorinated biphenyl (PCB) concentrations both differed for 50% of the biochemical measures. Associations between biochemical measures and delta15N-derived trophic position and/or contaminant levels in tissues suggest the effects may be toxicopathic responses. Associations were most frequently with PCBs and dioxin-like contaminants. The health of adult herring gulls varied with breeding location and "lifestyle" in the early 1990s, and Great Lakes gulls suffered from chemical and nutritional stressors that modulated physiological processes and endocrine function.


Asunto(s)
Biomarcadores/análisis , Charadriiformes/fisiología , Contaminantes Ambientales/análisis , Animales , Océano Atlántico , Citocromo P-450 CYP1A1/metabolismo , Monitoreo del Ambiente , Contaminantes Ambientales/efectos adversos , Femenino , Cadena Alimentaria , Great Lakes Region , Hígado/enzimología , Masculino , Estado Nutricional , Bifenilos Policlorados/efectos adversos , Bifenilos Policlorados/análisis , Reproducción
6.
J Toxicol Environ Health A ; 70(17): 1471-91, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17687731

RESUMEN

Organosomatic indices, hematological indicators of stress, and histopathological lesions were quantified for over 150 incubating herring gulls (Larus argentatus) sampled in 11 colonies throughout the Great Lakes and reference colonies in Lake Winnipeg and the Bay of Fundy. Of 21 parameters assessed, significantly more differed between Great Lakes colonies and reference colonies than between the two reference colonies. Relative adrenal, kidney, and liver masses of gulls from some Great Lakes colonies were reduced and thyroid masses increased relative to gulls from reference colonies. Foci of cellular atypia were observed in the hepatocytes of two Great Lakes gulls. Chronic periportal hepatitis, lipogranulomas and vacuolation of hepatocytes, and chronic granulomatous interstitial nephritis were more prevalent or severe in gulls from Great Lakes colonies and were associated with contaminants. The kidneys of gulls from the three most contaminated locations were damaged and functionally compromised. Interstitial nephritis was likely the most functionally significant histopathological lesion. Portal-tract fibrosis, granulomatous hepatitis, and kidney tubule dilation/obstruction and splenic enlargement were more prevalent or severe at reference sites and were associated with blood-borne parasites. Amyloid deposits were observed in the spleen, kidneys, or liver of nearly half of the gulls. Associations between the prevalence or severity of lesions and contaminant levels in gull tissues or the trophic level of their diet suggest some lesions are toxicopathic. Associations were most frequently found with planar halogenated aromatic hydrocarbons and lead. The stress response, as measured by the heterophil/lymphocyte ratio, was attenuated in gulls from Areas of Concern and associated with decreased adrenal mass. Our findings suggest that adult Great Lakes gulls suffered from chronic exposure to chemical stressors in the early 1990s sufficient to modulate endocrine function and physiological processes and induce structural changes in tissues.


Asunto(s)
Enfermedades de las Aves/patología , Charadriiformes/fisiología , Reproducción , Animales , Océano Atlántico , Biomarcadores/análisis , Ecosistema , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Contaminantes Ambientales/metabolismo , Femenino , Great Lakes Region , Historia del Siglo XX , Riñón/patología , Hígado/patología , Masculino , Bifenilos Policlorados/análisis , Bazo/patología
7.
Environ Toxicol Chem ; 26(9): 1896-903, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17702543

RESUMEN

Environmental pollution is ubiquitous and can pose a significant threat to wild populations through declines in fitness and population numbers. To elucidate the impact of marine pollution on a pelagic species, we assessed whether toxic contaminants accumulated in black-footed albatross (Phoebastria nigripes), a wide-ranging North Pacific predator, are correlated with altered physiological function. Blood samples from adult black-footed albatrosses on Midway Atoll, part of the Hawaiian (USA) archipelago, were analyzed for organochlorines (e.g., polychlorinated biphenyls [PCBs] and chlorinated pesticides), trace metals (silver, cadmium, tin, lead, chromium, nickel, copper, zinc, arsenic, selenium, and total mercury), and a sensitive physiological marker, peripheral white blood cell immune function (mitogen-induced lymphocyte proliferation and macrophage phagocytosis). We found a positive significant relationship between organochlorines, which were highly correlated within individual birds (p < 0.001, r > 0.80, Spearman correlation for all comparisons; PCBs, 160 +/- 60 ng/ml plasma [mean +/- standard deviation]; DDTs, 140 +/- 180 ng/ml plasma; chlordanes, 7.0 +/- 3.6 ng/ml plasma; hexachlorobenzene, 2.4 +/- 1.5 ng/ml plasma; n = 15) and increased lymphocyte proliferation (p = 0.020) as well as percentage lymphocytes (p = 0.033). Mercury was elevated in black-footed albatrosses (4,500 +/- 870 ng/ml whole blood, n = 15), and high mercury levels appeared to be associated (p = 0.017) with impaired macrophage phagocytosis. The associations we documented between multiple contaminant concentrations and immune function in endangered black-footed albatrosses provide some of the first evidence that albatrosses in the North Pacific may be affected by environmental contamination. Our results raise concern regarding detrimental health effects in pelagic predators exposed to persistent marine pollutants.


Asunto(s)
Aves/inmunología , Contaminantes Químicos del Agua/toxicidad , Envejecimiento/fisiología , Animales , Aves/sangre , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Color , Femenino , Salud , Linfocitos/efectos de los fármacos , Masculino , Fagocitos/efectos de los fármacos
8.
Environ Toxicol Chem ; 26(7): 1460-9, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17665687

RESUMEN

We conducted a dose-response laboratory study to quantify the level of exposure to dietary Hg, delivered as methylmercury chloride (CH3HgCl), that is associated with suppressed immune function in captive-reared common loon (Gavia immer) chicks. We used the phytohemagglutinin (PHA) skin test to assess T-lymphocyte function and the sheep red blood cell (SRBC) hemagglutination test to measure antibody-mediated immunity. The PHA stimulation index among chicks receiving dietary Hg treatment did not differ significantly from those of chicks on the control diet (p = 0.15). Total antibody (immunoglobulin [Ig] M [primary antibody] + IgG [secondary response]) production to the SRBC antigen in chicks treated with dietary methylmercury (MeHg), however, was suppressed (p = 0.04) relative to chicks on control diets. Analysis indicated suppression of total Ig production (p = 0.025 with comparisonwise alpha level = 0.017) between control and 0.4 microg Hg/g wet food intake treatment groups. Furthermore, the control group exhibited a higher degree of variability in antibody response compared to the Hg groups, suggesting that in addition to reducing the mean response, Hg treatment reduced the normal variation attributable to other biological factors. We observed bursal lymphoid depletion in chicks receiving the 1.2 microg Hg/g treatment (p = 0.017) and a marginally significant effect (p = 0.025) in chicks receiving the 0.4 microg Hg/g diet. These findings suggest that common loon chick immune systems may be compromised at an ecologically relevant dietary exposure concentration (0.4 microg Hg/g wet wt food intake). We also found that chicks hatched from eggs collected from low-pH lakes exhibited higher levels of lymphoid depletion in bursa tissue relative to chicks hatched from eggs collected from neutral-pH lakes.


Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Animales , Aves , Espectrofotometría Ultravioleta
9.
Artículo en Inglés | MEDLINE | ID: mdl-17446141

RESUMEN

Little is known about the correlations between biotransformation enzymes in juvenile birds after exposure to environmental toxicants like PCBs. In this study eggs of domestic chicken (Gallus domesticus) were dosed with PCB126 in concentrations of 0.175-0.325 ng/g egg weight. Liver subcellular fractions were analyzed for activities of Phase 1 and Phase 2 biotransformation enzymes 2 and 5 weeks post-hatch. Ethoxyresorufin O-deethylase (EROD) activity was increased in both the 2-week and 5-week samples. Glutathione-S-transferase (GST) activity was increased in the 2-week samples only, but the 5-week samples showed an overall much higher GST activity, probably as a result of a still developing enzyme expression in maturing chickens. The same pattern was seen in the phenol-type UDP-glucuronosyltransferase (UGT) activity of the control animals. The week two samples showed a positive dose-response relationship for the UGT activity, but after 5 weeks this was reversed, possibly caused by inhibition of hydroxylated PCB metabolites. Phenol-type sulfotransferase (SULT) activities were not significantly correlated with time or dose. There was a strong positive regression between the Ah-receptor mediated EROD and UGT activities. The EROD activities were also positively correlated to the GST activities. Most interesting was a negative correlation between the UGT and SULT activities: an inhibited UGT activity appeared to be compensated by an increased SULT activity.


Asunto(s)
Citocromo P-450 CYP1A1/metabolismo , Antagonistas de Estrógenos/toxicidad , Bifenilos Policlorados/toxicidad , Transferasas/metabolismo , Animales , Biotransformación , Embrión de Pollo , Pollos , Relación Dosis-Respuesta a Droga , Antagonistas de Estrógenos/farmacocinética , Glucuronosiltransferasa/metabolismo , Glutatión Transferasa/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Bifenilos Policlorados/farmacocinética , Sulfotransferasas/metabolismo
10.
Environ Pollut ; 138(3): 485-93, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15951077

RESUMEN

We investigated whether exposure to environmentally relevant polybrominated diphenyl ethers (PBDEs) causes immunomodulation in captive nestling American kestrels (Falco sparverius). Eggs within each clutch, divided by laying sequence, were injected with safflower oil or penta-BDE congeners-47, -99, -100, and -153 dissolved in safflower oil (18.7 microg sigmaPBDEs/egg) approximating Great Lakes birds. For 29 days, nestlings consumed the same PBDE mixture (15.6+/-0.3 ng/g body weight per day), reaching sigmaPBDE body burden concentrations that were 120x higher in the treatment birds (86.1+/-29.1 ng/g ww) than controls (0.73+/-0.5 ng/g ww). PBDE-exposed birds had a greater PHA response (T-cell-mediated immunity), which was negatively associated with increasing BDE-47 concentrations, but a reduced antibody-mediated response that was positively associated with increasing BDE-183 concentrations. There were also structural changes in the spleen (fewer germinal centers), bursa (reduced apoptosis) and thymus (increased macrophages), and negative associations between the spleen somatic index and sigmaPBDEs, and the bursa somatic index and BDE-47. Immunomodulation from PBDE exposure may be exacerbated in wild birds experiencing greater environmental stresses.


Asunto(s)
Contaminantes Ambientales/toxicidad , Falconiformes/inmunología , Éteres Fenílicos/toxicidad , Bifenilos Polibrominados/toxicidad , Animales , Formación de Anticuerpos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Bolsa de Fabricio/efectos de los fármacos , Bolsa de Fabricio/inmunología , Bolsa de Fabricio/patología , Exposición a Riesgos Ambientales/efectos adversos , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/análisis , Éteres Difenilos Halogenados , Inmunidad Celular/efectos de los fármacos , Macrófagos/inmunología , Óvulo/efectos de los fármacos , Óvulo/inmunología , Éteres Fenílicos/análisis , Bifenilos Polibrominados/análisis , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Timo/efectos de los fármacos , Timo/inmunología , Timo/patología
11.
J Toxicol Environ Health A ; 68(6): 485-500, 2005 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-15799247

RESUMEN

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyl (PCB) 126 produce thymic atrophy and immunosuppression. This study explored the hypothesis that the thymic atrophy produced by developmental exposure to PCB 126 is associated with an increase in apoptotic thymocytes at the end of incubation in chicken embryos. Eggs were injected via the air cell with PCB 126 (0.05, 0.13, 0.32, 0.64, and 0.80 ng/g egg) on d 0 of incubation, and tissues were collected on d 20. Controls included noninjected and vehicle-injected (sunflower oil) eggs. Thymocytes were cultured for 6 h and analyzed by flow cytometry for decreased DNA content (propidium iodide staining) and cell size (forward scatter), which indicate apoptosis. PCB 126 induced dose-dependent mortality with an LD50 of 1.01 ng/g and lowest-observed-effect concentration (LOEC) of 0.32 ng/g. Teratogenic effects commonly associated with TCDD and planar PCBs, including cranial and foot deformities and subcutaneous edema, tended to increase with dose of PCB 126. PCB 126 reduced thymus mass by approximately 20% at 0.64 and 0.8 ng/g, the number of viable thymocytes by approximately 20-24% at and above 0.13 ng/g, and the number of bursal lymphoid cells by 57% at 0.64 ng/g. The percentage of apoptotic thymocytes increased with dose, reaching levels 2 times greater than controls at 0.8 ng/g. Electrophoresis of low-molecular-weight DNA from thymocytes of all doses demonstrated fragments in multiples of 180 bp. This DNA laddering is a hallmark of apoptosis. At all doses, thymocytes exhibited caspase-3 activation, another indicator of apoptosis. The results of this experiment supported the hypothesis that the thymic atrophy produced by developmental exposure to PCB 126 in chicken embryos is associated with an increase in apoptotic thymocytes on embryonic d 20.


Asunto(s)
Apoptosis/efectos de los fármacos , Antagonistas de Estrógenos/toxicidad , Bifenilos Policlorados/toxicidad , Timo/citología , Timo/patología , Animales , Atrofia , Técnicas de Cultivo de Célula , Embrión de Pollo , Pollos , Daño del ADN , Relación Dosis-Respuesta a Droga
12.
Toxicology ; 204(1): 23-40, 2004 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-15369846

RESUMEN

Microcystin-LR is a cyanobacterial heptapeptide that presents acute and chronic hazards to animal and human health. We investigated the influence of this toxin on human and chicken immune system modulation in vitro. Peripheral blood lymphocytes were treated with microcystin-LR at environmentally relevant doses of 1, 10 and 25 microg/ml for 12, 24, 48, 72 h (for proliferation assay cells were treated for 72 h). T-cell and B-cell proliferation as well as apoptosis and necrosis were determined in human and chicken samples. IL-2 and IL-6 production by human lymphocytes also was measured. In addition, uptake kinetics of microcystin-LR into human and chicken peripheral blood lymphocytes were calculated by Liquid Chromatography (LS) /Mass Spectrometry (MS) analysis. At the highest dose microcystin-LR decreased T-cell proliferation and all doses of microcystin-LR inhibited B-cell proliferation. The frequency of apoptotic and necrotic cells increased in a dose and time-dependent manner. Human lymphocytes responded to stimulation with microcystin-LR by increased production of IL-6 and decreased production of IL-2. Human lymphocytes were able to uptake from 0.014 to 1.663 microg/ml and chicken lymphocytes from 0.035 to 1.733 microg/ml of the microcystin-LR added to the cultures, depending on the treatment time and dose. In conclusion, microcystin-LR acted as an immunomodulator in cytokine production and down-regulated lymphocyte functions by induction of apoptosis and necrosis. However, further studies dealing with the influence of microcystin-LR on expression cytokine genes and transcription factors are necessary to confirm these hypotheses.


Asunto(s)
Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Toxinas Marinas/farmacocinética , Toxinas Marinas/toxicidad , Péptidos Cíclicos/farmacocinética , Péptidos Cíclicos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Linfocitos B/efectos de los fármacos , División Celular/efectos de los fármacos , Cromatografía Liquida , Femenino , Humanos , Técnicas In Vitro , Interleucina-2/biosíntesis , Interleucina-6/biosíntesis , Espectrometría de Masas/métodos , Microcistinas , Necrosis , Fosfatidilserinas/metabolismo , Linfocitos T/efectos de los fármacos
13.
Toxicology ; 183(1-3): 175-97, 2003 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-12504350

RESUMEN

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.


Asunto(s)
Compuestos Epoxi/toxicidad , Grafito/toxicidad , Neumonía/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Lesión por Inhalación de Humo/fisiopatología , Animales , Líquido del Lavado Bronquioalveolar/química , Quimiocina CXCL2 , Modelos Animales de Enfermedad , Herbicidas/toxicidad , Histocitoquímica , Interferón gamma/biosíntesis , Masculino , Monocinas/biosíntesis , Paraquat/toxicidad , Neumonía/etiología , Neumonía/metabolismo , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/metabolismo , Pruebas de Función Respiratoria , Humo/efectos adversos , Lesión por Inhalación de Humo/etiología , Lesión por Inhalación de Humo/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis
14.
Integr Comp Biol ; 42(1): 34-42, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21708692

RESUMEN

Laboratory and field studies have demonstrated that the immune system is sensitive to environmental contaminants. Testing protocols have been developed to screen for immunotoxic effects and elucidate mechanisms of toxicity in laboratory rodents. Similar methods have been applied to wildlife species in captivity and the wild. Several epizootics in wildlife have been associated with elevated exposure to contaminants. This paper discusses immunotoxicological techniques used in studies of avian wildlife. Measurements of immunological structure include peripheral white blood cell counts and the mass and cellularity of immune organs such as the thymus, spleen, and bursa of Fabricius. While contaminants can alter these measures of immunological structure, such measures do not directly assess how the immune system functions, i.e., responds to specific challenges. The two most commonly used in vivo immune function tests in birds are the phytohemagglutinin (PHA) skin response for T cell-mediated immunity and the sheep red blood cell (SRBC) hemagglutination assay for antibody-mediated immunity. In vitro tests of immune function in avian wildlife include proliferation of lymphocytes in response to various mitogens and phagocytosis of fluorescent particles by monocytes. While optimization of in vitro techniques for wildlife species is often time-consuming, these assays usually require only a single blood sample and can elucidate mechanisms of toxicity. In immunological studies of wildlife, investigators should consider factors that may influence immune responses, including age, body condition, date, developmental stage of the immune system, and time required for the progression of immune responses.

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