Valutazione degli effetti immunotossici di diverse micotossine in linfociti di suino e macrofagi murini.
Russo, Rosario (2010) Valutazione degli effetti immunotossici di diverse micotossine in linfociti di suino e macrofagi murini. [Tesi di dottorato] (Inedito)
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Mycotoxins are secondary metabolites produced by microfungi mainly belonging to Aspergillus spp., Fusarium spp. and Penicillium spp. frequently found as contaminants in many food products especially of vegetable origin. The climate change we have seen in recent years and the import of raw materials from developing countries have contributed to the global nature of the problem of food contamination by mycotoxins. They are a heterogeneous group of chemicals that can lead to a broad spectrum of toxic effects in humans and animals. Many mycotoxins exert mutagenic, carcinogenic, teratogenic and immunotoxic properties. It is particularly interesting the capacity of some mycotoxins to alter normal immune response when they are present in food at levels below the ones necessary for the manifestation of clinical symptoms of mycotoxicosis. However, while the immunomodulatory effects exerted by several mycotoxins have been demonstrated both in vivo and in vitro, few studies have been carried out to date to assess the toxic effects exerted by several mycotoxins simultaneously present in the same food substrate. Therefore, in the current work we have chosen to use immuno-competent cells such as porcine whole blood lymphocytes and murine macrophages (J774A.1 cells) as experimental models in order to evaluate the immunomodulatory activity of fumonisin B1 (FB1), α-zearalenolo (α-ZEA), deoxynivalenol (DON), nivalenolo (NIV), aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin M1 (AFM1) and aflatoxin M2 (AFM2), alone or differently combined (1:1 ratio). In this study, we demonstrated the cytotoxic effect exerted by different mycotoxins (α-ZEA, DON, NIV, AFB1), individually and differently combined, in porcine lymphocytes and in J774A.1 murine macrophages. We have also shown that, in the latter cell model, NIV showed a greater cytotoxic effect than DON; moreover, AFB1 and AFB2 possess antiproliferative activity not shown by their hydroxylated metabolites, AFM1 and AFM2, respectively. However, the immunotoxic effects of the aflatoxins evaluated in the current study may be due to the inhibition of production of active oxygen metabolites such as NO. We also investigated the mechanisms underlying the toxicity of these mycotoxins demonstrating that the antiproliferative activity shown by both trichothecenes, NIV and DON, in murine macrophages may be partly attributed to an acceleration of the apoptotic pathway that involves an increased activation of ERK protein, the induction of pro-apoptotic protein Bax, the activation of caspase-3 and cleavage of DNA repair enzyme, PARP-1. In addition, NIV and DON caused a cell cycle arrest in G0/G1 phase while AFB1 was responsible for an increase in S-phase cell population. Currently, studies are being carried out to better understand the mechanisms underlying the immunotoxicity of these mycotoxins, because the data available in literature are still few if compared to the strong impact these contaminants have on both human and animal health, in particular, underlining the potential risks arising from the co-contamination of multiple mycotoxins, very common condition which has not been taken into account yet as of now.
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