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Possible applications of zebrafish inflammatory models in toxicology research
Boda Zsófia - year 5
University of Veterinary Medicine Budapest, Department of Food Hygiene
Supervisors: Bence Ivánovics, József Lehel

Abstract:

Due to anthropogenic activities increasing amounts of environmental pollutants enter the environment A potential target for these xenobiotics is the immune system, which plays a vital role in host defense against pathogens. Impairment of this system can result in several short- and long-term health consequences.

The aim of this thesis was to provide an overview of zebrafish models which are based on the induction of local or systemic inflammation, and to investigate the immuno-toxicological effects of embryonic exposure to sublethal concentrations of bendiocarb, a carbamate insecticide. The effects of embryonic exposure to sublethal concentrations of bendiocarb were investigated on the distribution and abundance of neutrophil granulocytes and on the production of an inflammatory mediator, nitric oxide. The expression of certain immune- and inflammation-associated marker genes on bendiocarb-exposed zebrafish embryos was also investigated. In addition, we evaluated the modulatory effects of embryonic bendiocarb-exposure on neutrophil granulocyte response and function using local and LPS-induced systemic inflammatory models.

The exposure to bendiocarb resulted in a diffuse, widespread distribution of neutrophil granulocytes in the whole embryos, and a significant increase in neutrophil accumulation along the lateral line in a concentration-dependent manner. An elevated nitric oxide production has also been observed along the lateral line. Furthermore, bendiocarb-exposure resulted in significant up-regulation of immune- and inflammation-associated marker genes. In addition, in the tail fin transection model, neutrophil granulocyte migration to the wound site showed a significant, concentration-dependent decrease after bendiocarb-exposure. Interestingly, during the intense systemic inflammation induced by LPS treatment, neutrophil granulocytes showed a greater tolerance to LPS in the embryos, which were previously exposed to bendiocarb.

Overall, it can be concluded that the sublethal, embryonic exposure to bendiocarb induced pro-inflammatory effects in the zebrafish embryos, presumably as part of the result of potentially damaged neuromasts along the lateral line. The response of neutrophil granulocytes to a local and a systemic inflammation was also strongly affected by the embryonic exposure. In conclusion, these findings indicate a significant immunomodulatory potential of this carbamate insecticide. The result of our study draws attention to the need of further, more detailed studies focusing on the investigation of short- and long-term immunological consequences of embryonic bendiocarb-exposure.



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