| 体外研究 |
Triphenyl phosphate (10-100 μM; 48 h) dose dependently inhibits the migration of MC3T3-E1 osteoblasts [1].
Triphenyl phosphate (0-100 μM; 24-120 h) dose - and time-dependent decreased the proliferation ability and survival rate of MC3T3-E1 osteoblasts [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) can inhibit the MEK/ERK axis of the MAPK signaling pathway in MC3T3-E1 osteoblasts and alter the expression of EMT related proteins, and these effects can be reversed by MEK/ERK activation [1].
Triphenyl phosphate (40 μM; 48 h) can downregulate the expression of NR3C1, IGF1R, MAP3K1, BRAF, WNK4, and CNR2 genes in MC3T3-E1 osteoblasts [1].
Triphenyl phosphate (50-150 μM) can significantly increase ROS levels in H9c2 cardiomyocytes [2].
Triphenyl phosphate (150 μM) can reduce the fluorescence intensity of MitoTracker Red in H9c2 cardiomyocytes, indicating impaired mitochondrial morphology [2].
Triphenyl phosphate (150 μM) can enhance the fluorescence intensity of LysoTracker Green in H9c2 cardiomyocytes, indicating changes in lysosomal activity [2].
Triphenyl phosphate (150 μM) can significantly reduce the proportion of cells with high mitochondrial membrane potential in H9c2 cardiomyocytes [2].
Triphenyl phosphate (150 μM) can upregulate the expression of mitochondrial autophagy related proteins Parkin, Pink1, and LC3II/I in H9c2 cardiomyocytes [2].
Triphenyl phosphate (150 μM) can significantly increase the apoptosis rate of H9c2 cardiomyocytes [2].
Triphenyl phosphate (3.3-33 μM; 48 h) can activate NF κ B through MAOA mediated oxidative stress, thereby interfering with tryptophan metabolism in human trophoblast JEG-3 cells. Relevant effects can be observed at concentrations as low as 3.3 μM for 48 h [3].
Triphenyl phosphate (10 μM; 10 days) can induce significant triglyceride accumulation and lipid droplet formation in 3T3-L1 preadipocytes undergoing differentiation [4].
Triphenyl phosphate (0.1-10 μM; 10 days) can promote adipogenic differentiation of 3T3-L1 preadipocytes, with a concentration of 10 μM significantly upregulating the expression of key adipogenic genes and proteins, and disrupting lipid homeostasis by enhancing lipid synthesis and lipolysis [4].
Triphenyl phosphate (10 μM; 10 days) can induce lipid metabolism disorders in differentiated 3T3-L1 preadipocytes, altering the levels of various lipid species and disrupting key metabolic pathways [4].
Triphenyl phosphate (10 μM; 10 days) can alter the global gene expression of 3T3-L1 preadipocytes during differentiation, activate the PPAR signaling pathway and fatty acid metabolism, thereby promoting lipid accumulation and adipocyte differentiation [4].
Triphenyl phosphate (10 μM; 10 days) can activate the PI3K/AKT signaling pathway in differentiated 3T3-L1 preadipocytes, and this activation is necessary for TPHP induced lipid accumulation and adipogenic differentiation, as inhibition with LY294002 can reverse these effects [4].
Cell Migration Assay
| Cell Line: |
murine pre-osteoblastic MC3T3-E1 cells |
| Concentration: |
10, 25, 50, 100 μM |
| Incubation Time: |
48 hours |
| Result: |
Inhibited MC3T3-E1 cell migration in a concentration-dependent manner, with significant reductions in migration rate observed at 10, 25, 50, and 100 μM compared to control. |
Cell Invasion Assay
| Cell Line: |
murine pre-osteoblastic MC3T3-E1 cells |
| Concentration: |
10, 20, 40 μM |
| Incubation Time: |
24 hours |
| Result: |
Significantly suppressed MC3T3-E1 cell invasion and migration in a concentration-dependent manner, with significant reductions in relative cell count observed at 10, 20, and 40 μM compared to control. |
Western Blot Analysis
| Cell Line: |
murine pre-osteoblastic MC3T3-E1 cells |
| Concentration: |
10, 20, 40 μM (single treatment); 40 μM (co-treatment with 1 μM C16-PAF or 10 μM MEK-IN-6 |
| Incubation Time: |
48 hours |
| Result: |
Significantly decreased phosphorylation levels of p-MEK and p-ERK1/2 (with no change to p-P38 or p-JNK), upregulated E-Cadherin expression, and downregulated N-Cadherin expression.
Reversed these changes when co-treated with the MEK/ERK activator C16-PAF, restoring p-MEK and p-ERK1/2 phosphorylation and normalizing E-Cadherin and N-Cadherin levels.
Did not reverse the effects when co-treated with MEK inhibitor MEK-IN-6. |
Real Time qPCR
| Cell Line: |
murine pre-osteoblastic MC3T3-E1 cells |
| Concentration: |
40 μM |
| Incubation Time: |
48 hours |
| Result: |
Significantly downregulated the mRNA expression levels of NR3C1, IGF1R, MAP3K1, BRAF, WNK4, and CNR2 compared to the control group. |
|
| 体内研究 |
Triphenyl phosphate (5-50 mg/kg; oral; Daily; Continuous exposure for 30 days can induce dose-dependent cardiac toxicity in C57BL/6 J mice, with a dose of 50 mg/kg causing significant cardiac fibrosis, oxidative stress, mitochondrial dysfunction, mitochondrial autophagy, and cardiomyocyte apoptosis [2].
Triphenyl phosphate (0.5-2 mg/kg; oral; Daily; Pregnancy from day 0 to day 12 can induce placental oxidative stress in pregnant C57BL/6 mice, activate inflammatory factors, and disrupt tryptophan metabolism [3].
Triphenyl phosphate (1-150 mg/kg; oral; Once a day; For 60 consecutive days, it can induce gender specific lipid metabolism disorders and promote obesity in male mice by dose dependently increasing the coefficient of inguinal adipose tissue, promoting adipocyte hypertrophy, and upregulating genes related to lipid and lipid metabolism, but has no significant effect on the morphology of adipose tissue in female mice [4].
Triphenyl phosphate (1-500 μg/L; exposed to potassium solution; 72 hours) can induce concentration dependent reproductive toxicity in Caenorhabditis elegans by disrupting the JNK signaling pathway.
Triphenyl phosphate (0.89-9.19 μg/kg; oral; Once a day; At 28 weeks, female BALB/c mice were induced to exhibit significant anxiety like and depression like behaviors by disrupting the gut brain axis, including dysbiosis of the gut microbiota, systemic oxidative stress and inflammatory response, as well as metabolic and signaling pathway disorders in the prefrontal cortex.
| Animal Model: |
C57BL/6 J (adult male, 20-25 g) |
| Dosage: |
5 mg/kg; 50 mg/kg |
| Administration: |
p.o.; daily; 30 days |
| Result: |
Induced disordered myocardial cell arrangement and increased eosinophilic cardiomyocytes at 50 mg/kg.
Elevated serum creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) levels significantly at 50 mg/kg.
Increased heart malondialdehyde (MDA) levels, while decreased superoxide dismutase (SOD) and serum glutathione peroxidase (GSH-Px) activities at 50 mg/kg.
Caused irregular cardiomyocyte mitochondrial shapes and disordered cristae at 50 mg/kg.
Decreased protein expression of mitochondrial fusion/fission factors (Mfn1, Mfn2, Opa1, Drp1, Fis1) significantly at 50 mg/kg.
Induced autophagosomes in cardiomyocytes, with increased protein expression of Parkin, Pink1, and LC3II/I at 50 mg/kg.
Increased TUNEL-positive apoptotic cardiomyocytes at 50 mg/kg.
Increased protein expression of Bax, CytC, and Cleaved-Caspase 3, decreased Bcl-2 expression, and increased Cleaved-Caspase 9 expression at 50 mg/kg.
Increased cardiac collagen deposition, with increased protein expression of Wnt, β-catenin, p-β-catenin, collagen I, collagen III, CTGF, and fibronectin at 50 mg/kg.
Showed no significant changes in myocardial histopathology, serum CK-MB/LDH levels, oxidative stress markers, mitochondrial structure/factor expression, or cardiac fibrosis markers at 5 mg/kg.
Increased Cleaved-Caspase 9 protein expression significantly, with no change in TUNEL-positive apoptotic cells at 5 mg/kg. |
|
| Animal Model: |
C57BL/6 (6-8 weeks old, female, pregnant) |
| Dosage: |
0.5 mg/kg; 1 mg/kg; 2 mg/kg |
| Administration: |
p.o.; daily; E0 to E12 |
| Result: |
Increased placental GSH to ~100 μmol/g, MDA to ~4 nmol/mgprot, and SOD vitality to ~150 U/mgprot at 2 mg/kg.
Increased placental MDA to ~3 nmol/mgprot and decreased SOD vitality to ~100 U/mgprot at 1 mg/kg.
Increased placental NFκB, IL6, MAOA, and KYNU gene expression, and decreased TPH1 and DDC gene expression at 0.5 mg/kg.
Increased placental NFκB, TNFα, IL6, MAOA, KYNU, and IDO1 gene expression, and decreased TPH1 and DDC gene expression at 1 mg/kg.
Increased placental NFκB, TNFα, IL6, MAOA, KMO, and KYNU gene expression, and decreased TPH1 and DDC gene expression at 2 mg/kg.
Increased placental NFκB, IDO1, and MAOA protein expression, and decreased TPH1 protein expression at 0.5 mg/kg.
Increased placental NFκB, TNFα, IL6, IDO1, TDO2, and MAOA protein expression, and decreased TPH1 protein expression at 1 mg/kg.
Increased placental NFκB, TNFα, IL6, IDO1, TDO2, and MAOA protein expression, and decreased TPH1 protein expression at 2 mg/kg.
Decreased placental tryptophan to ~25 μg/g FW and 5-HTP to ~0.015 μg/g FW at 1 mg/kg.
Increased placental serotonin to ~0.15 μg/g FW, 5-HIAA to ~0.3 μg/g FW, and KYN to ~25 μg/g FW at 1 mg/kg.
Showed a trend toward increased 3-HK levels at 1 mg/kg. |
| Animal Model: |
BALB/c (male, female, 3 weeks old at study start, oral exposure to triphenyl phosphate for 60 days to induce lipid metabolism disorder) |
| Dosage: |
1 mg/kg/day; 10 mg/kg/day; 150 mg/kg/day |
| Administration: |
p.o.; daily; 60 days |
| Result: |
Increased inguinal adipose tissue coefficient in a dose-dependent manner in male mice.
Induced significant adipocyte hypertrophy across all doses in male mice, with mean adipocyte area significantly larger than control.
Increased serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in male mice treated with 150 mg/kg/day, while all doses reduced serum triglyceride (TG) levels in male mice.
Upregulated PPARγ mRNA expression in a dose-dependent manner in male mice.
Upregulated chemerin mRNA expression in male mice treated with 150 mg/kg/day.
Upregulated lipid synthesis-related genes (Pck1, PDK, ChERBP) and lipolytic genes (Lipe, MGL) in male mice.
Showed an upward trend in serum TG, TC, HDL-C, and low-density lipoprotein cholesterol (LDL-C) levels in female mice treated with 150 mg/kg/day, with no significant changes in inguinal adipose tissue coefficient or adipocyte size compared to control. |
| Animal Model: |
wild-type Bristol N2; MT1079/egl-15 (n484) X; VC1089/mkk-4 (ok1545) X; VC822/kgb-2 (gk361) IV; JT366/vhp-1(sa366) II (synchronized L1-stage larvae) |
| Dosage: |
1 μg/L, 10 μg/L, 100 μg/L, 500 μg/L |
| Administration: |
exposure in K+ solution; daily feeding; 72 hours |
| Result: |
Reduced mean lifespan by 1.65% (1 μg/L), 12.47% (10 μg/L), 13.3% (100 μg/L), and 25.22% (500 μg/L) relative to controls.
Determined 10-day LC50 as 575.47 μg/L (95% CI: 450.58-819.39 μg/L).
Reduced germ cell counts in the mitotic zone, transition zone, and meiotic prophase by 37.5%/41.0% (1 μg/L/500 μg/L), 30.2%/28.9%, and 36.9%/38.5% respectively.
Increased gonadal apoptotic cell count by 17.2% (1 μg/L), 77.6% (10 μg/L), 133.2% (100 μg/L), and 138.9% (500 μg/L) relative to controls.
Reduced uterine embryo count by 14.2% (1 μg/L), 18.2% (10 μg/L), 18.1% (100 μg/L), and 21.8% (500 μg/L) relative to controls.
Reduced total progeny count by 10.66% (1 μg/L), 13.94% (10 μg/L), 15.25% (100 μg/L), and 17.39% (500 μg/L) relative to controls.
Downregulated transcript levels of egl-15, dlk-1, mkk-4, kgb-2, and vhp-1, while upregulated kgb-1 in 500 μg/L exposed wild-type worms.
Increased gonadal apoptotic cell counts significantly higher than in exposed wild-type worms, and reduced uterine embryo counts and total progeny counts significantly lower than in exposed wild-type worms in mutant strains exposed to 1 μg/L or 500 μg/L TPHP. |
| Animal Model: |
BALB/c (female, 3 weeks old, 15−18 g) |
| Dosage: |
0.89 μg/kg/day; 9.19 μg/kg/day |
| Administration: |
p.o.; daily; 28 weeks |
| Result: |
Reduced distance traveled in the central area by 67.8%, reduced time spent moving in the central area by 64.1%, significantly reduced upright behavior count, and significantly reduced grooming behavior count (9.19 μg/kg/day, open field test).
Reduced open arm entry frequency by 2.1-fold, reduced open arm retention time by 84.1% (9.19 μg/kg/day, elevated plus maze test).
Reduced sucrose preference index by 40.1% (9.19 μg/kg/day, sucrose preference test).
Reduced uric acid levels, reduced 5-hydroxytryptophan levels, elevated quinolinic acid levels, elevated glutamate levels, significantly elevated reactive oxygen species, nitric oxide, and malondialdehyde levels, upregulated catalase and superoxide dismutase expression, and increased NF-κB p65 and pro-inflammatory factors (TNF-α, IL-1β, IL-6) (9.19 μg/kg/day, prefrontal cortex).
Decreased relative abundance of Bacteroidota, increased Firmicutes, significantly reduced relative abundance of norank_f_Muribaculaceae, Lactobacillus, Alloprevotella, Bacteroides, and g_Akkermansia, significantly increased Lachnospiraceae_NK4A136_group, significantly increased Chao1 index, and showed β-diversity compositional differences from controls (9.19 μg/kg/day, gut microbiota).
Reduced xanthine levels, elevated uric acid levels, reduced 5-hydroxytryptophan levels, and significantly reduced acetic acid, propionic acid, and butyric acid levels.
Significantly upregulated quinolinic acid and glutamate levels, significantly downregulated xanthine, 5-hydroxytryptophan, acetic acid, propionic acid, and butyric acid levels, significantly elevated reactive oxygen species, nitric oxide, malondialdehyde, TNF-α, IL-1β, IL-6, and NF-κB p65 levels, and reached a mean level of 2.09 ng/mL (9.19 μg/kg/day, serum).
Significantly reduced time spent moving in the central area and reduced upright behavior count (0.89 μg/kg/day, open field test).
Showed 1208 upregulated and 1382 downregulated genes relative to controls, altered NF-κB signaling pathway and leukocyte transendothelial migration pathways, and disrupted purine and tryptophan metabolism pathways with trends matching the high-dose group (0.89 μg/kg/day, prefrontal cortex).
Mirrored high-dose group trends but most changes were not statistically significant (0.89 μg/kg/day, gut microbiota).
Reached a mean level of 0.36 ng/mL (0.89 μg/kg/day, serum). |
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Data Sheet