The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and adaptative immune response. Weaned pigs were fed for 18 days with a control or a ZEA contaminated diet. The effect of ZEA was assessed on wide genome expression, pro- (TNF-α, IL-8, IL-6, IL-1β, IFN-γ) and anti-inflammatory (IL-10, IL-4) cytokines, other molecules involved in inflammatory processes (MMPs/TIMPs), as well as signaling molecules, (p38/JNK1/JNK2-MAPKs) and nuclear receptors (PPARγ/NFkB/AP-1/STAT3/c-JUN). Microarray analysis showed that 46% of total number of differentially expressed genes was involved in cellular signaling pathway, 13% in cytokine network and 10% in the inflammatory response. ZEA increased expression and synthesis of pro- inflammatory (TNF-α, IL-8, IL-6, IL-1β) and had no effect on IFN-γ, IL-4 and IL-10 cytokines in spleen. The inflammatory stimulation might be a consequence of JNK pathway activation rather than of p-38MAPK and NF-kB involvement whose gene and protein expression were suppressed by ZEA action. In summary, our findings indicated the role of ZEA as an immune disruptor at spleen level.
Ochratoxins, are toxic fungal metabolites produced by certain moulds of the genera Aspergillus and Penicillium that grow on a wide range of raw food commodities. The most relevant toxin is ochratoxin A (OTA) and the European Commission has established guidance values for OTA concerning complementary and complete feeding stuff recommending that for pigs a maximum concentration of 0.05 mg/kg. These guidance values represent only a recommendation of the Commission and the establishment of a legal regulation needs additional toxicological data generated from farm animal experiments. The aim of this paper was to investigate the effect of OTA – at the recommended EU guidance value of 0.05 mg/kg – on liver health. For this purpose, twelve crossbred, weaned piglets were fed for 33 days a maize-soybean-meal-based diet contaminated or not with 0.05 mg/kg OTA. Blood plasma samples were collected at the end of this period and subjected to biochemical analyses, whereas liver samples were analysed for cytokine concentration (ELISA), enzyme activity and expression of selected genes (qRT-PCR) involved in liver metabolism. Exposure to OTA resulted in a significant decrease in the concentrations of total protein, albumin and nitric oxide in plasma, and interleukin-6 in the liver. OTA exposure also resulted in a significant increase of alanine aminotransferase and triglycerides in plasma and of superoxide dismutase in the liver. In conclusion, the administration of 0.05 mg/kg of OTA, to weaned piglets for a period of 33 days caused measurable hepatocellular injury in the toxin-exposed. Additional in vivo studies should be performed with larger numbers of animals in order to confirm our results and to provide robust data for the establishment of safe concentrations of OTA in swine feeds.
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