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1.
Int J Mol Sci ; 16(12): 29417-35, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26690409

RESUMO

The biochemical and histopathological changes induced by the exposure to iron oxide nanoparticles coated with phospholipid-based polymeric micelles (IONPs-PM) in CD-1 mice lungs were analyzed. After 2, 3, 7 and 14 days following the intravenous injection of IONPs-PM (5 and 15 mg Fe/kg bw), lactate dehydrogenase (LDH) activity, oxidative stress parameters and the expression of Bax, Bcl-2, caspase-3 and TNF-α were evaluated in lung tissue. An increase of catalase (CAT) and glutathione reductase (GR) activities on the second day followed by a decrease on the seventh day, as well as a decline of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity on the third and seventh day were observed in treated groups vs. controls. However, all these enzymatic activities almost fully recovered on the 14th day. The reduced glutathione (GSH) and protein thiols levels decreased significantly in nanoparticles-treated groups and remained diminished during the entire experimental period; by contrast malondialdehyde (MDA) and protein carbonyls increased between the 3rd and 14th day of treatment vs. control. Relevant histopathological modifications were highlighted using Hematoxylin and Eosin (H&E) staining. In addition, major changes in the expression of apoptosis markers were observed in the first week, more pronounced for the higher dose. The injected IONPs-PM generated a dose-dependent decrease of the mouse lung capacity, which counteracted oxidative stress, thus creating circumstances for morphopathological lesions and oxidation processes.


Assuntos
Pulmão/patologia , Nanopartículas de Magnetita/toxicidade , Estresse Oxidativo , Fosfatidiletanolaminas/toxicidade , Polietilenoglicóis/toxicidade , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos , Pulmão/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Micelas , Tamanho da Partícula , Carbonilação Proteica
2.
Toxicol Lett ; 232(1): 310-25, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25455459

RESUMO

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-1ß, 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.


Assuntos
Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Perfilação da Expressão Gênica/métodos , Concentração Inibidora 50 , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Fatores de Tempo
3.
Int J Mol Sci ; 13(8): 10193-10211, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22949855

RESUMO

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development.


Assuntos
Carpas/metabolismo , Rim/química , Rim/metabolismo , Estresse Oxidativo , Pontos Quânticos , Silício/administração & dosagem , Silício/química , Animais , Carpas/crescimento & desenvolvimento , Catalase/química , Glutationa/metabolismo , Glutationa Peroxidase/química , Glutationa Redutase/química , Glutationa Transferase/química , Rim/citologia , Peroxidação de Lipídeos , Oxirredução , Superóxido Dismutase/química
4.
Br J Nutr ; 95(6): 1185-92, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16768843

RESUMO

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides, a fungus that commonly contaminates maize. Sex-related effects of FB1 have been observed with respect to carcinogenicity in rodents, to performances in pigs and immunosuppression in mice. In the present study the sex-related effect of FB1 on the pig immune response was determined. Female and castrated male piglets received for 28 d either control feed or feed contaminated with 8 mg FB1/kg feed in the form of F. verticillioides culture material. At day 7 and day 21, animals were immunised subcutaneously with a Mycoplasma agalactiae vaccine. Ingestion of FB1-contaminated feed significantly decreased weight gain in males but had no effect in females. No sex-related difference was observed in biochemical parameters, but a higher level of creatinine was noted in toxin-treated animals. FB1 also altered the pig immune response in a sex-specific manner. In males, ingestion of FB1-contaminated feed significantly decreased specific antibody levels after vaccination as well as the mRNA expression level of IL-10. In females, the toxin has no effect on specific antibodies or on cytokine mRNA levels. The results of the present study indicate that FB1 is immunosuppressive in pigs. The magnitude of this FB1-induced immunosuppression is highly dependent on sex, with males being more susceptible than females.


Assuntos
Contaminação de Alimentos , Microbiologia de Alimentos , Fumonisinas/efeitos adversos , Micotoxinas/efeitos adversos , Suínos/imunologia , Ração Animal , Animais , Anticorpos Antibacterianos/sangue , Citocinas/genética , Feminino , Terapia de Imunossupressão , Masculino , Mycoplasma agalactiae/imunologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , Suínos/metabolismo , Vacinação , Zea mays/microbiologia
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