RESUMO
Diabetes mellitus (DM) is a metabolic disorder that causes severe complications in several tissues due to redox imbalances, which in turn cause defective angiogenesis in response to ischemia and activate a number of proinflammatory pathways. Our study aimed to investigate the effect of bee gomogenat (BG) dietary supplementation on the architecture of immune organs in a streptozotocin (STZ)-induced type 1 diabetes (T1D) mouse model. Three animal groups were used: the control non-diabetic, diabetic, and BG-treated diabetic groups. STZ-induced diabetes was associated with increased levels of blood glucose, ROS, and IL-6 and decreased levels of IL-2, IL-7, IL-4, and GSH. Moreover, diabetic mice showed alterations in the expression of autophagy markers (LC3, Beclin-1, and P62) and apoptosis markers (Bcl-2 and Bax) in the thymus, spleen, and lymph nodes. Most importantly, the phosphorylation level of AKT (a promoter of cell survival) was significantly decreased, but the expression levels of MCP-1 and HSP-70 (markers of inflammation) were significantly increased in the spleen and lymph nodes in diabetic mice compared to control animals. Interestingly, oral supplementation with BG restored the levels of blood glucose, ROS, IL-6, IL-2, IL-4, IL-7, and GSH in diabetic mice. Treatment with BG significantly abrogated apoptosis and autophagy in lymphoid organs in diabetic mice by restoring the expression levels of LC3, Beclin-1, P62, Bcl-2, and Bax; decreasing inflammatory signals by downregulating the expression of MCP-1 and HSP-70; and promoting cell survival by enhancing the phosphorylation of AKT. Our data were the first to reveal the therapeutic potential of BG on the architecture of lymphoid organs and enhancing the immune system during T1D.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animais , Apoptose , Autofagia , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Abelhas , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Interleucina-6/metabolismo , Interleucina-7/metabolismo , Interleucina-7/farmacologia , Interleucina-7/uso terapêutico , Camundongos , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Proteína X Associada a bcl-2/metabolismoRESUMO
The surveillance and virological characterization of H5N8 avian influenza viruses are important in order to assess their zoonotic potential. The genetic analyses of the Egyptian H5N8 viruses isolated through active surveillance in wild birds and domestic poultry in the winter of 2016/2017 showed multiple introductions of reassortant viruses. In this study, we investigated and compared the growth kinetics, infectivity, and pathogenicity of the three reassortant forms of H5N8 viruses detected in wild birds and domestic poultry in Egypt during the first introduction wave in the winter of 2016/2017. Three representative H5N8 viruses (abbreviated as 813, 871, and 13666) were selected. The 871/H5N8 virus showed enhanced growth properties in vitro in Madin Darby canine kidney (MDCK) and A549 cells. Interestingly, all viruses replicated well in mice without prior adaptation. Infected C57BL/6 mice showed 20% mortality for 813/H5N8 and 60% mortality for 871/H5N8 and 13666/H5N8, which could be attributed to the genetic differences among the viruses. Studies on the pathogenicity in experimentally infected ducks revealed a range of pathogenic effects, with mortality rate ranging from 0% for 813/H5N8 and 13666/H5N8 to 28% for 871/H5N8. No significant differences were observed among the three compared viruses in infected chickens. Overall, different H5N8 viruses had variable biological characteristics, indicating a continuous need for surveillance and virus characterization efforts.