Selenium mitigates the inhibitory effect of TBBPA on NETs release by regulating ROS/MAPK pathways-induced carp neutrophil apoptosis and necroptosis.

Tetrabromobisphenol A (TBBPA) is one of the most common and persistent organic pollutants found in the environment. When TBBPA is ingested by organisms through various pathways and stored in the body, it shows obvious harmful effects. Selenium (Se) works as an antioxidant in the body, allowing it to withstand the poisonous effects of dangerous substances. The effects and mechanisms of Se and TBBPA on carp neutrophil immune function, apoptosis, and necroptosis, however, are unknown. As a result, we created TBBPA exposure and Se antagonism models using carp neutrophils as study objects, and we investigated the expression of genes implicated in extracellular traps (NETs), cytokines, apoptosis, and necroptosis. The findings demonstrated that extracellular traps neutrophils in the TBBPA group displayed the inhibition of NETs, apoptosis, and necrosis, as well as an increase in Reactive oxygen species (ROS) levels and activation of the MAPK pathway. The expression of genes related to the mitochondrial apoptosis pathway (Bax, Cyt-c, Bcl-2 and Caspase-3) and necroptosis pathway (MLKL, RIPK1, RIPK3, Caspase-8 and FADD) were activated. The expression of inflammatory factors IL-1 and TNF-α were increased, and the expression of IL-2 and IFN-γ were decreased. But an appropriate concentration of Se can mitigate the effects of TBBPA. Our results suggest that Se can mitigate the inhibitory effect of TBBPA on NETs release by regulating apoptosis and necroptosis of carp neutrophil via ROS/MAPK pathways. These results provide a basis information for exploring the toxicity of TBBPA, and enrich the anti-toxicity mechanism of trace element Se in the body.

Bisphenol A exacerbates selenium deficiency-induced pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway in chicken trachea.

Selenium deficiency can lead to multiple tissue and organ damage in the body and could coexist with chronic toxic exposures. Contamination from Bisphenol A (BPA) exposure can induce the occurrence of various injuries including pyroptosis. However, it is not clear whether selenium deficiency and BPA exposure affect tracheal tissue pyroptosis in chickens. To investigate whether selenium deficiency and BPA exposure induce chicken tracheal tissue pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway and the effect of their combined exposure on tissue injury, we developed a model of relevant chicken tracheal injury. Sixty broilers were divided into four groups: the control group (C group), selenium-deficient group (SeD group), BPA-exposed group (BPA group) and combined exposure group (SeD + BPA group). The study examined the expression indicators of markers of pyroptosis (NLRP3&GSDMD), NF-κB pathway-related inflammatory factors (NF-κB, iNOS, TNF-α, COX-2), pyroptosis-related factors (ASC, Caspase-1, IL-1ß, IL-18), and some heat shock proteins and interleukins (HSP60, HSP90, IL-6, IL-17) in the samples. The results showed that the expression of the above indicators was significantly upregulated in the different treatment groups (P < 0.05). In addition, the expression levels of the above related indicators were more significantly up-regulated in the combined selenium-deficient and BPA-exposed group compared to the group in which they were individually exposed. It was concluded that selenium deficiency and BPA exposure induced tracheal tissue pyroptosis in chickens through NF-κB/NLRP3/Caspase-1 pathway, and BPA exposure exacerbated selenium deficiency-induced tracheal pyroptosis. The present study provides new ideas into studies related to the co-exposure of organismal micronutrient deficiency and chronic toxicants.