Triphenyl phosphate

Triphenyl phosphate is an orally active, blood-brain barrier-permeable aryl organophosphate flame retardant and endocrine disruptor. Triphenyl phosphate disrupts mitochondrial dynamic balance through oxidative stress, induces excessive mitophagy and apoptosis, and ultimately leads to myocardial fibrosis. In the brain, Triphenyl phosphate activates the NF-κB inflammatory pathway by disrupting the gut microbiota, alters tryptophan metabolism and elevates neurotoxins, thereby inducing anxiety- and depression-like behaviors. In the skeletal and reproductive systems, Triphenyl phosphate inhibits osteoblast differentiation and induces germ cell apoptosis by suppressing the MAPK/ERK pathway and activating the JNK signal, respectively. In adipose and placental tissues, Triphenyl phosphate promotes lipid accumulation by activating the PI3K/AKT-PPARγ axis, and disrupts placental metabolism via the MAOA/ROS/NF-κB cascade, impairing neurodevelopment of offspring^{[1][2][3][4][6]}. In Vitro:Triphenyl phosphate (10-100 μM; 48 h) inhibits the migration of MC3T3-E1 osteoblasts in a dose-dependent manner^[1].
Triphenyl phosphate (0-100 μM; 24-120 h) reduces the proliferation capacity and survival rate of MC3T3-E1 osteoblasts in a dose- and time-dependent manner^[1].
Triphenyl phosphate (10-40 μM; 24 h) dose-dependently inhibits the invasion and migration of MC3T3-E1 osteoblasts^[1].
Triphenyl phosphate (10-40 μM; 48 h) inhibits the MEK/ERK axis of the MAPK signaling pathway in MC3T3-E1 osteoblasts and alters the expression of EMT-related proteins, and these effects are reversed by MEK/ERK activation^[1].
Triphenyl phosphate (40 μM; 48 h) downregulates the expression of NR3C1, IGF1R, MAP3K1, BRAF, WNK4 and CNR2 genes in MC3T3-E1 osteoblasts^[1].
Triphenyl phosphate (50-150 μM) significantly increases the intracellular ROS level in H9c2 cardiomyocytes^[2].
Triphenyl phosphate (150 μM) reduces the fluorescence intensity of MitoTracker Red in H9c2 cardiomyocytes, indicating impaired mitochondrial morphology^[2].
Triphenyl phosphate (150 μM) increases the fluorescence intensity of LysoTracker Green in H9c2 cardiomyocytes, indicating altered lysosomal activity^[2].
Triphenyl phosphate (150 μM) significantly reduces the proportion of cells with high mitochondrial membrane potential in H9c2 cardiomyocytes^[2].
Triphenyl phosphate (150 μM) upregulates the expression of mitophagy-related proteins Parkin, Pink1, and LC3II/I in H9c2 cardiomyocytes^[2].
Triphenyl phosphate (150 μM) significantly increases the apoptosis rate of H9c2 cardiomyocytes^[2].
Triphenyl phosphate (3.3-33 μM; 48 h) interferes with tryptophan metabolism in human trophoblast JEG-3 cells by activating NF-κB via MAOA-mediated oxidative stress, and the relevant effect is observable even at a concentration as low as 3.3 μM after 48 h of exposure^[3].
Triphenyl phosphate (10 μM; 10 days) induces significant triglyceride accumulation and lipid droplet formation in differentiating 3T3-L1 preadipocytes^[4].
Triphenyl phosphate (0.1-10 μM; 10 days) promotes adipogenic differentiation of 3T3-L1 preadipocytes. Specifically, the 10 μM concentration significantly upregulates the expression of key adipogenic genes and proteins, and disrupts lipid homeostasis by enhancing lipogenesis and lipolysis^[4].
Triphenyl phosphate (10 μM; 10 days) induces lipid metabolism disorder in differentiating 3T3-L1 preadipocytes, alters the levels of multiple lipid species, and disrupts key metabolic pathways^[4].
Triphenyl phosphate (10 μM; 10 days) alters global gene expression in differentiating 3T3-L1 preadipocytes, activates the PPAR signaling pathway and fatty acid metabolism, thereby promoting lipid accumulation and adipocyte differentiation^[4].
Triphenyl phosphate (10 μM; 10 days) activates the PI3K/AKT signaling pathway in differentiating 3T3-L1 preadipocytes, and this activation is essential for TPHP-induced lipid accumulation and adipogenic differentiation, as inhibition with LY294002 reverses these effects^[4]. In Vivo:Triphenyl phosphate (5-50 mg/kg; p.o.; daily; for consecutive 30 days) induces dose-dependent cardiotoxicity in C57BL/6 J mice, and the 50 mg/kg dose triggers significant cardiac fibrosis, oxidative stress, mitochondrial dysfunction, mitophagy and cardiomyocyte apoptosis^[2].
Triphenyl phosphate (0.5-2 mg/kg; p.o.; daily; from gestational day 0 to gestational day 12) induces placental oxidative stress, activates inflammatory cytokines, and disrupts tryptophan metabolism in pregnant C57BL/6 mice^[3].
Triphenyl phosphate (1-150 mg/kg; p.o.; once daily; for consecutive 60 days) induces sex-specific lipid metabolism disorders, and promotes obesity in male mice by dose-dependently increasing the inguinal adipose tissue coefficient, promoting adipocyte hypertrophy, and upregulating adipogenesis- and lipid metabolism-related genes, but exerts no significant effect on adipose tissue morphology in female mice^[4].
Triphenyl phosphate (1-500 μg/L; exposed in potassium solution; 72 h) induces concentration-dependent reproductive toxicity in *Caenorhabditis elegans* by disrupting the JNK signaling pathway^[5].
Triphenyl phosphate (0.89-9.19 μg/kg; p.o.; once daily; 28 weeks) induces significant anxiety-like and depression-like behaviors in female BALB/c mice by disrupting the gut-brain axis, including intestinal dysbiosis, systemic oxidative stress and inflammatory responses, as well as metabolic and signaling pathway disorders in the prefrontal cortex^[6].