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1.
Food Chem Toxicol ; 153: 112247, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33951485

RESUMEN

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium molds. Grain-based foods account for most human dietary exposures to OTA. OTA is a teratogen, but its reproductive and developmental effects are poorly understood. A one-generation reproductive toxicity study was conducted with groups of 16 male and 16 female Fischer rats exposed to 0, 0.026, 0.064, 0.16, 0.4 or 1.0 mg OTA/kg in diet. Dams exposed to 1.0 mg OTA/kg diet had statistically significant F1 pup losses between implantation and postnatal day (PND 4). Delays in preputial separation (PPS) and vaginal opening (VO) were indicative of delayed puberty in F1 rats. Mild renal lesions in nursing pups indicated that exposure prior to weaning impacted the kidneys. The developing kidney was more susceptible to OTA than the adult kidney. Significant increases in multi-oocyte follicles (MOFs) and proportional changes in resting and growing follicles were observed in F1 female ovaries. Plasma testosterone was reduced in F0 males, and there were negative effects on sperm quality in F0 and F1 male rats. The results confirm that continuous dietary exposure to OTA causes post-implantation fetotoxicity in dams, and renal and reproductive toxicity in their male and female offspring.


Asunto(s)
Blastocisto/efectos de los fármacos , Infertilidad Femenina/inducido químicamente , Infertilidad Masculina/inducido químicamente , Enfermedades Renales/inducido químicamente , Ocratoxinas/toxicidad , Motilidad Espermática/efectos de los fármacos , Animales , Animales Lactantes , Bloqueadores de los Canales de Calcio/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ocratoxinas/administración & dosificación , Folículo Ovárico/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Endogámicas F344
2.
Toxicol Pathol ; 38(4): 619-30, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20530249

RESUMEN

Rodent studies have shown that furan is a hepatocarcinogen. Previous studies conducted with high doses showed tumors at nearly 100% incidence at all doses. In this paper, a ninety-day gavage experiment conducted with lower doses (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg bw) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including gross changes and histopathology, clinical biochemistry, hematology, and immunotoxicology is reported. As indicated by changes in serum biomarkers, increased liver weights and gross and histological lesions, the liver is the major target organ affected by furan. There were no changes in body weights, food consumption, or histology in other organs. Some of the serum electrolyte markers, including phosphorus, were altered. There was a significant increase in serum thyroxine and triidothyronine in males. This increase was not accompanied by histological thyroid changes. Immunophenotypic analysis showed that thymic lymphocyte maturation was altered in male rats. Although altered clinical biochemistry and hematological parameters were observed at a dose of > 0.5 mg/kg bw, mild histological lesions in the liver were observed at > 0.12 mg/kg bw. Based on this finding, a furan dose of 0.03 mg/kg bw was proposed as the no-observed adverse effect level for hepatic toxicity.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Furanos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Análisis de Varianza , Animales , Biomarcadores/sangre , Plaquetas/metabolismo , Peso Corporal/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Dieta , Femenino , Furanos/administración & dosificación , Histocitoquímica , Incidencia , Hígado/patología , Pruebas de Función Hepática , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Linfocitos T/metabolismo
3.
Diabetologia ; 48(8): 1576-84, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16003532

RESUMEN

AIMS/HYPOTHESIS: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetes-prone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat protein-induced Th1 cell activation. METHODS: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. RESULTS: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3(+)CD4(+)IFN-gamma(+) T cells were more prevalent in the MLN of wheat-fed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3(+)CD4(+) T cells. This proliferation was associated with a low proportion of CD4(+)CD25(+) T cells and a high proportion of dendritic cells in the MLN of BBdp rats. CONCLUSIONS/INTERPRETATION: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.


Asunto(s)
Diabetes Mellitus/inmunología , Ganglios Linfáticos/inmunología , Proteínas de Plantas/farmacología , Células TH1/efectos de los fármacos , Triticum/química , Animales , Células Presentadoras de Antígenos/efectos de los fármacos , Antígenos CD4/biosíntesis , Proliferación Celular/efectos de los fármacos , Citocinas/farmacología , Proteínas de Unión al ADN/genética , Dieta , Citometría de Flujo , Factor de Transcripción GATA3 , Indicadores y Reactivos , Interferón gamma/biosíntesis , Ganglios Linfáticos/efectos de los fármacos , Mesenterio/efectos de los fármacos , Mesenterio/inmunología , Fenotipo , Ratas , Ratas Endogámicas BB , Bazo/citología , Bazo/efectos de los fármacos , Proteínas de Dominio T Box/biosíntesis , Proteínas de Dominio T Box/genética , Células Th2/efectos de los fármacos , Transactivadores/genética
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