Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells

Abstract

The predominant reliance on bromated flame retardants (BFRs) is diminishing with expanded use of alternative organophosphate flame retardants. However, exposure related issues for susceptible populations, the developing, infirmed, or aged, remain given environmental persistence and home environment detection. In this regard, reports of flame retardant (FR)-related effects on the innate immune system suggest process by which a spectrum of adverse health effects could manifest across the life-span. As representative of the nervous system innate immune system, the current study examined changes in microglia following exposure to representative FRs, pentabromophenol (PBP), tetrabromobisphenol A (2,2',6,6',-tetrabromo-4,4'-isopropylidine diphenol; TBBPA) and triphenyl phosphate (TPP). Following 18hr exposure of murine BV-2 cells, at dose levels resulting in ≥80% viability (10 and 40μM), limited alterations in pro-inflammatory responses were observed however, changes were observed in mitochondrial respiration. Basal respiration was altered by PBP; ATP-linked respiration by PBP and TBBPA, and maximum respiration by all three FRs. Basal glycolytic rate was altered by PBP and TBBPA and compensatory glycolysis by all three. Phagocytosis was decreased for PBP and TBBPA. NLRP3 inflammasome activation was assessed using BV-2-ASC (apoptosis-associated speck-like protein containing a CARD) reporter cells to

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

“…While the function of the NLRP3 inflammasome in astrocytes is controversial, it is known to be expressed and activated in microglia (Gustin et al, 2015;Freeman and Guo, 2017;Slowik et al, 2018). Evidence shows that pentabromophenol (PBP) and tetrabromobisphenol A (TBBPA) improves the metabolic rate of glycolysis in mouse microglia and promotes the activation of NLRP3 inflammasome (Bowen et al, 2020). Hexokinase is one of the key glycolytic enzymes.…”

Development of in vitro test methods in a model of human pancreatic β-cells to identify metabolism disrupting chemicals with diabetogenic activity

“…This agrees with our results, in which 1 μM TCS did not change β-cell viability. Despite the lack of evidence in pancreatic β-cells, it has been shown that exposure to high doses of TPP and DDE (>10 μM) induced apoptosis in other cells and tissues: TPP in hepatocytes, epithelial tumoral JEG-3 cells from placenta, and murine BV-2 microglia [53–55]; and DDE in Sertoli cells [56,57]. Exposure to high concentrations of p,p’ -DDT (>150 μM) for 24 h decreased viability in NES2Y human pancreatic β-cell line [58].…”

Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

“…Microglia also exploit glycolysis to maintain the immune functional response [ 23 ]. In particular, enhancing glycolytic flux in the microglia promotes inflammasome activation [ 24 ]. Glucose 6-phosphate (G6P) can be channeled into the pentose phosphate pathway (PPP) [ 25 ], which promotes the two-step oxidative decarboxylation of G6P catalyzed by glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), yielding ribulose-5-phosphate (R5P).…”