Seneca Valley virus induces immunodepressionin suckling piglets by selective apoptosis of B lymphocytes.

Seneca Valley virus (SVV) is the causative agent of an emerging infectious vesicular disease in swine that is clinically indistinguishable from other vesicular diseases of swine. This study utilized healthy suckling piglets (control) and SVV-naturally infected suckling piglets to determine the effects of SVV on lymphoid tissues and determined the SVV RNA load by quantitative RT-PCR (qRT-PCR). Furthermore, immunohistochemistry (IHC) analyses were performed to quantify the expression of T and B cell lymphocytes, natural killer cells, cleaved caspase 3, and ki-67. The main histopathologic finding in the infected group was severe lymphoid depletion. The highest average of SVV RNA load by qRT-PCR (Log10 genomic copies/g of tissue) occurred at the spleen (8.54 ± 0.8), followed by the tonsils (8.04 ± 1.42), and mesenteric lymph nodes (6.90 ± 1.42). The IHC analyses revealed that there was an increased in cellular apoptosis with concomitant reduction in the proliferation of B cells. The results from this study have demonstrated that SVV-infected piglets exhibited decreased lymphocyte density probably due to lymphoid apoptosis, affecting particularly B-cells lymphocytes.

Ovarian toxicity by fusariotoxins in pigs: Does it imply in oxidative stress?

Mycotoxins are natural contaminants of food and feed occurring worldwide. Deoxynivalenol (DON) and fumonisin B1 (FB1) are the most frequent fusariotoxins and induce immune and intestinal toxicity in humans and animals. Recently, an association between mycotoxins exposure and impaired fertility has been suggested. However, the effects of these mycotoxins on the reproductive system are not well established. This study aimed to evaluate the effects of FB1 and DON, in combination or alone, on the ovarian morphology and oxidative responses using porcine explants. Seventy-two explants were obtained from six pigs and submitted to the following treatments: control (MEM medium), DON (10 µM), FB1 (100 µM FB1), and DON + FB1 (10 µM + 100 µM). Histological and immunohistochemical assays were performed to evaluate ovarian changes, cell proliferation, and apoptosis. Oxidative stress response was evaluated through lipid peroxidation and antioxidant capacity response assays. The exposure to mycotoxins induced significant histological changes in the ovaries, which were characterized by a decrease in viable follicles and increase in degenerated follicles. A significant decrease in granulosa cell proliferation was observed in explants exposed to all mycotoxins. In addition the multi-contaminated treatment was responsible for an increase in the cell apoptosis index of growing follicles. On the other hand, the FB1 and multi-contaminated treatments induced a significant decrease in lipid peroxidation accompanied by an increase in antioxidant responses. Altogether, our results indicate a reproductive toxicity induced by fusariotoxins. Moreover, mycotoxins, alone or in combination, modulate oxidative stress response, interfering with the production of free radicals and affecting the reproductive capacity of pigs.

Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways.

The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.

Os efeitos do farelo de aveia e da farinha de soja na resposta imune humoral de ratos alimentados com dieta hipercolesterolêmica / The effects of oat bran and soy flour on humoral immune response in rats fed hypercholesterolaemic diets

Estudos anteriores têm demonstrado os efeitos sobre o sistema imune e sobre os níveis de colesterol da dieta com fibra solúvel e proteína de soja em ratos. Nesse estudo, nós avaliamos os efeitos do farelo de aveia e da farinha de soja na resposta imune humoral de ratos Wistar tratados com dietas hipercolesterolêmicas. Os animais (6 grupos) foram alimentados com diferentes dietas por 6 semanas e inoculados duas vezes com antígeno (IgY). As amostras de plasma foram coletadas após cada inoculação e os níveis de anticorpos anti-IgY (IgM, IgG1 e IgG2a) foram avaliados por ELISA. Os animais que receberam 1% de colesterol apresentaram um aumento de IgG1 anti-IgY e uma redução de IgM e IgG2a anti-IgY em relação aos animais controle. Estes efeitos foram anulados em animais alimentados com 1% de colesterol e farelo de aveia ou aveia + proteína de soja, mas não em animais alimentados com 1% de colesterol e proteína de soja. As dietas contendo 1% de colesterol resultaram em lesões hepáticas e aumentaram o peso relativo do fígado e do baço, mas não afetaram o perfil lipídico, o ganho de peso e o consumo de alimentos ou eficiência na conversão alimentar. Em conclusão, uma dieta com alto teor de colesterol influencia na produção de classes de anticorpos em resposta a um antígeno de forma que pode ser revertida pelo farelo de aveia.

Previous studies have demonstrated the immunological and hypercholesterolaemic effects of soluble dietary fibre and soy protein in rats. In this study, we evaluated the effects of oat bran and soy flour on humoral immune response in Wistar rats fed hypercholesterolaemic diets. Animals (6 groups) fed with different diets for 6 wks were inoculated twice with antigen (IgY). Plasma samples were collected after each inoculation and anti-IgY antibody (IgM, IgG1 and IgG2a) levels were evaluated by ELISA. Animals receiving 1% cholesterol presented an increase in anti-IgY IgG1 and a reduction in anti-IgY IgM and IgG2a relative to control animals. These effects were abrogated in animals fed 1% cholesterol and oat bran or oat bran+soy protein, but not in animals fed 1% cholesterol and soy protein. Diets containing 1% cholesterol resulted in hepatic lesions and higher liver and spleen relative weights, but did not affect lipid profile, weight gain, food intake, or food conversion efficiency. In conclusion, a high-cholesterol diet influences classes of antibodies produced in response to an antigen in a way that can be reversed by oat bran

Deoxynivalenol induces toxic effects in the ovaries of pigs: An ex vivo approach.

Deoxynivalenol (DON) is a frequently found trichothecene mycotoxin that elicits toxic effects on humans and animals. In pigs, DON induces changes in digestive and immune systems. Effects on the reproductive system are scarce and mainly based in in vitro models. The aim of this study was to evaluate, using an ex vivo model, the effects of DON on the morphology of ovaries of pigs in all stages of follicular development. Six 5-month-old pigs were used for sampling the explants. Thirty-six explants were incubated for 48 hours in culture medium (n = 18) or medium containing 10 µM of DON (n = 18). After the incubation period, the explants were submitted to histologic and immunohistochemical (proliferating cell nuclear antigen [PCNA] expression) analysis. Histologic changes were scored, and a lesional score was established. Oocytes and follicular cells immunostained for PCNA were counted. Explants exposed to DON showed a significant increase in the lesional score (P = 0.0004) compared to control explants. The main histologic changes were degeneration of oocytes and granulosa cells, interstitial edema and pyknotic cells. DON induced a reduction in the number of normal follicles in all stages of follicular development: primordial (P = 0.005), primary (P = 0.04), and growing follicles (P = 0.04) compared to control group. Deoxynivalenol also induced a significant increase (P ≤ 0.05) in the number of pyknotic oocytes in all stages of follicular development; however, no significant change in PCNA expression in oocytes or follicular cells was observed. These results indicated that DON induces toxic effects on the ovaries, affecting follicular development and interfering with reproductive parameters on pigs. Also, the present data indicate that ovarian explants are an adequate model for assessing reproductive toxicity.

Phytic acid decreases deoxynivalenol and fumonisin B1-induced changes on swine jejunal explants.

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters on intestinal explants exposed to deoxynivalenol (DON) and fumonisin B1 (FB1). The jejunal explants were exposed for 4 h to different treatments: control, DON (10 µM), DON plus 2.5 mM or 5 mM IP6, FB1 (70 µM), and FB1 plus 2.5 mM or 5 mM IP6. Both mycotoxins induced significant intestinal lesions and decreased villi height. The presence of 2.5 mM and 5 mM IP6 significantly inhibited the morphological changes caused by the mycotoxins. DON induced a significant increase in caspase-3 (83%) and cyclooxygenase-2 (71.3%) expression compared with the control. The presence of 5 mM IP6 induced a significant decrease in caspase-3 (43.7%) and Cox-2 (48%) expression compared with the DON group. FB1 induced a significant increase in caspase-3 expression (47%) compared to the control, whereas IP6 induced no significant change in this expression. A significant decrease in cell proliferation was observed when explants were exposed to 5 mM of IP6 in comparison with the DON and FB1 groups. The present data provide evidence that phytic acid modulates the toxic effects induced by DON and FB1 on intestinal tissue.

Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.

This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.