Postnatal development of intestinal immune system in piglets: implications for the process of weaning

European-wide directives are in place to establish a sustainable production of pigs without using production enhancers and chemotherapeutics. Thus, an economically-viable pig production is now only possible when the physiological mechanisms of defense against pathogens and tolerance against nutrients and commensal bacteria in the intestinal immune system are taken into account. During the postnatal period the piglet is facing first the time large amounts of new antigens and at weaning a second wave of nutritional antigens is entering the intestinal tract. The appropriate development of humoral and cellular functions of the intestinal immune system is essential for optimum growth and performance of the piglets. The integrity of the intestinal surfaces is a prerequisite of intestinal immunity and tolerance. Secretory IgA serves to exclude harmful antigens from uptake. The induction of intestinal immune reactions starts with antigen presentation by professional antigen presenting cells of Peyer's patches and mesenteric lymph nodes. In addition, the intestinal lamina propria serves as a mucosal compartment for regulation of immune responses. Here especially T regulatory cells (CD4(+) CD25(+)) have their function for maintaining intestinal homeostasis. The network of mucosal T and B cells develops after birth in a programmed sequence; it is almost completed at week 7 after birth. Weaning is associated with changes in the regulation of the lymphoid cells in the mucosa. In small and large intestine increases in pro- and anti-inflammatory cytokines were observed after weaning in lymphocytes. Epithelial cells were studied both in intestinal samples and in vitro. Here the cytokine patterns provide evidence that weaning is inducing a transient inflammation of the mucosa. Piglets weaned under conventional conditions have a thicker mucosa than pigs weaned from isolators. Cells of isolator-reared pigs show slightly higher levels of activation markers - probably reflecting the interaction of the foreign protein derived from bovine milk. The results presented in this overview demonstrate that further effort is necessary to elucidate the function of the porcine intestinal immune system in the postnatal period and at the time of weaning to provide criteria for porcine intestinal health

Quantificação de citocinas no soro e homogenato da pata na intoxicação experimental com veneno de Bothropoides jararaca em ratos Wistar tratados com soroterapia e Mikania glomerata

This experiment aimed to quantify the pro-inflammatory cytokine levels, including TNF-α, interleukin-1β (IL-1β) and IL-6 as well as the anti-inflammatory ones such as IL-10 and INF-γ. It was also proposed to compare the effect of the conventional treatment to a treatment in which was added the Mikania glomerata plant in the experimental intoxication using Bothropoides jararaca venom. It was used Wistar rats that were randomly divided into 3 groups: C - control; VB - Bothrops venom + antivenom serum; and VBM - Bothrops venom + antivenom serum + Mikania glomerata. Cytokines were quantified in the serum and paw homogenate using ELISA test in three different moments (M1- 30 minutes, M2- 6 hours and M3- 24 hours after venom injection). The intoxication by Bothropoides jararaca venoms mainly stimulated the production of IL-6 in the serum and TNF-α, IL-1β, IL-6 in paw homogenate of animals experimentally intoxicated. Adjunctive treatment with the extract of the Mikania glomerata plant mainly influenced the production of IL-6, IL-10 and IFN-γ in the serum and IL-6, IL1β and IFN-γ in paw homogenate. Further research is necessary with the extract of Mikania glomerata in order to understand the action of this plant on the Bothropoides poisoning and also to verify the best way to manage it.O presente estudo teve como objetivo quantificar os níveis de citocinas pró-inflamatórias, entre as quais TNF-α, interleucina-1β (IL-1β), IL-6, e anti-inflamatórias, como IL-10, interferon-γ (INF-γ), bem como comparar o efeito do tratamento convencional com o efeito do tratamento complementado pelo extrato da planta Mikania glomerata, na intoxicação experimental por Bothropoides jararaca. Foram usados ratos Wistar,divididos em três grupos: C - controle, VB - veneno botrópico + soro antiofídico e VBM - veneno botrópico + soro antiofídico + Mikania glomerata. As citocinas foram quantificadas, no soro e no homogenato desses animais, pelo teste ELISA, em três momentos (M1 - 30 minutos, M2 - seis horas e M3 - 24 horas após a inoculação do veneno). Os resultados obtidos evidenciaram que a intoxicação por veneno botrópico estimula principalmente a produção de IL-6 no soro e TNF-α, IL-1β, IL-6 no homogenato da pata de animais experimentalmente intoxicados. O tratamento complementar, com o extrato da planta Mikania glomerata, teve influência principalmente na produção de IL-6, IL-10 e IFN-γ no soro e IL-6, IL-1β e IFN-γ no homogenato. Porém, são necessários novos estudos com o extrato de Mikania glomerata para que se possa entender a ação dessa planta sobre a intoxicação botrópica, bem como verificar qual a melhor via para administrá-lo.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Unesp Faculdade de Medicina Veterinária e ZootecniaUnoeste Faculdade de Ciências AgráriasUnesp Instituto de Biociência de BotucatuUnesp Faculdade de Medicina Veterinária e ZootecniaUnesp Instituto de Biociência de Botucat

The importance of accounting for sex in the search of proteomic signatures of mycotoxin exposure

International audienceMycotoxins are natural food and feed contaminants that are toxic to human and animals. Proteomics is an adequate toolbox to investigate the mode of action and the effects of mycotoxins, as these toxicants often alter protein synthesis and degradation, as well as induce changes of important post-translational modifications. For instance, the contaminant deoxynivalenol induces a severe ribosomal stress that affects protein production, whereas the toxin Fumonisin B1 can alter the phosphorylation of a large number of proteins, and patulin is a potent proteotoxic molecule. The response to most mycotoxins is sex-dependent, males being generally more sensitive than females. In addition, for some toxins, the toxic effects observed were different for each sex. Nevertheless, the importance of accounting for a sex-dependent response is often overlooked in toxicology studies involving mycotoxins. Here we review the information that proteomics has provided in pre-clinical studies of mycotoxin exposure as well as the differential response of males and females to these molecules to highlight the need of including male and female individuals when evaluating the impact of mycotoxins in the cell proteome

Toxins | Mycotoxins

International audienceMycotoxins are toxic secondary metabolites produced by many fungal species. They are frequent contaminants of many foods and feeds and especially cereals. More than 100 countries set up regulations for these natural contaminants to prevent toxicity in animals and humans. Many analytical methods are developed to assess contamination. Most of the official methods rely on liquid chromatography however the use of immunological tools allowed the development of rapid methods for screening purpose. Mass spectrometry is the method of choice for multi-mycotoxin analysis

Mycotoxins and oxidative stress: where are we?

Mycotoxins are the most common contaminants of food and feed worldwide and are considered an important risk factor for human and animal health. Oxidative stress occurs in cells when the concentration of reactive oxygen species exceeds the cell’s antioxidant capacity. Oxidative stress causes DNA damage, enhances lipid peroxidation, protein damage and cell death. This review addresses the toxicity of the major mycotoxins, especially aflatoxin B1, deoxynivalenol, nivalenol, T-2 toxin, fumonisin B1, ochratoxin, patulin and zearalenone, in relation to oxidative stress. It summarises the data associated with oxidative stress as a plausible mechanism for mycotoxin-induced toxicity. Given the contamination caused by mycotoxins worldwide, the protective effects of a variety of natural compounds due to their antioxidant capacities have been evaluated. We review data on the ability of vitamins, flavonoids, crocin, curcumin, green tea, lycopene, phytic acid, L-carnitine, melatonin, minerals and mixtures of anti-oxidants to mitigate the toxic effect of mycotoxins associated with oxidative stress. </jats:p

Deoxynivalenol in the liver and lymphoid organs of rats: effects of dose and duration on immunohistological changes

Deoxynivalenol (DON) is one of the most prevalent type B trichothecenes present in food inducing adverse effects, including intestinal changes and immunosuppression. The aim of the present study was to investigate the effects of DON on rats exposed for 7, 14 and 28 days to mycotoxin-contaminated diets, using histological and immunohistochemical analyses on liver and lymphoid organs. Fifty rats received a control diet, or a diet contaminated with 1.75 mg/kg of DON for 30 days, or a diet contaminated with 11.4 mg/kg of DON for 7, 14 or 30 days. Ingestion of contaminated feed induced a significant increase in the lesional score in the liver, spleen, and lymph nodes. The main histological findings observed in the liver were cytoplasmic vacuolisation and hepatocelular megalocytosis. A significant increase in hepatocyte proliferation was observed in rats that received 1.75 mg/kg of DON. Lymphoid depletion was the main histological alteration observed in lymphoid organs, resulting in a significant increase in the lesional score in all groups that received the contaminated diets. The histological changes and lymphocyte apoptosis were more severe in lymph nodes of rats fed 11.4 mg/kg of DON during 30 days. The results of the morphological and immunohistochemical analyses suggest that the ingestion of DON can induce functional hepatic impairment and immunosuppression in a dose- and time-dependent manner. </jats:p

Effect of various doses of deoxynivalenol on liver xenobiotic metabolizing enzymes in mice

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