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p-Methylphenyl potassium sulfate Sale

(Synonyms: 对甲基硫酸钾; p-Tolyl sulfate potassium; p-Cresyl sulfate potassium) 目录号 : GC31519

p-Methylphenyl potassium sulfate是一种与慢性肾病进展、心血管风险和死亡率相关的原型蛋白质结合尿毒症毒素,来源于肝脏的酪氨酸和苯丙氨酸代谢产物。

p-Methylphenyl potassium sulfate Chemical Structure

Cas No.:91978-69-7

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10mM (in 1mL DMSO)
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50mg
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Sample solution is provided at 25 µL, 10mM.

Description

p-Methylphenyl potassium sulfate is a prototype protein-binding uremic toxin associated with the progression of chronic kidney disease, cardiovascular risk and mortality, derived from tyrosine and phenylalanine metabolites in the liver[1,2]. The serum level of p-Methylphenyl potassium sulfate is associated with the progression of renal failure[3], cardiovascular risk and mortality[4]. The toxic mechanisms of p-Methylphenyl potassium sulfate include promoting inflammatory responses and causing endothelial dysfunction[5,6].

In vitro, primary osteoblasts were treated with p-Methylphenyl potassium sulfate (0.05, 0.125, 0.25, 0.5mM) for 24 hours by activating the c-Jun n-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways. It leads to the down-regulation of parathyroid hormone type 1 receptor (PTHR), thereby causing osteoblast dysfunction[7].

In vivo, p-Methylphenyl potassium sulfate (10mg/kg) was intraperitoneally injected into mice with chronic kidney disease (CKD) model induced by 5/6 nephrectomy. After being administered twice a day for 4 consecutive weeks, p-Methylphenyl potassium sulfate aggravates insulin resistance in CKD mice, directly activates (extracellular signal-regulated kinase 1/2) ERK1/2 kinase, and inhibits the insulin signaling pathway[8].

References:
[1]Smith EA, Macfarlane GT. Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. J Appl Bacteriol. 1996 Sep;81(3):288-302.
[2] Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2):52.
[3] Wu IW, Hsu KH, Lee CC, Sun CY, Hsu HJ, Tsai CJ, Tzen CY, Wang YC, Lin CY, Wu MS. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011 Mar;26(3):938-47.
[4] Liabeuf S, Barreto DV, Barreto FC, Meert N, Glorieux G, Schepers E, Temmar M, Choukroun G, Vanholder R, Massy ZA; European Uraemic Toxin Work Group (EUTox). Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transplant. 2010 Apr;25(4):1183-91.
[5] Schepers E, Meert N, Glorieux G, Goeman J, Van der Eycken J, Vanholder R. P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production. Nephrol Dial Transplant. 2007 Feb;22(2):592-6.
[6] Meijers BK, Van Kerckhoven S, Verbeke K, Dehaen W, Vanrenterghem Y, Hoylaerts MF, Evenepoel P. The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am J Kidney Dis. 2009 Nov;54(5):891-901.
[7] Tanaka H, Iwasaki Y, Yamato H, Mori Y, Komaba H, Watanabe H, Maruyama T, Fukagawa M. p-Cresyl sulfate induces osteoblast dysfunction through activating JNK and p38 MAPK pathways. Bone. 2013 Oct;56(2):347-54.
[8] Koppe L, Pillon NJ, Vella RE, Croze ML, Pelletier CC, Chambert S, Massy Z, Glorieux G, Vanholder R, Dugenet Y, Soula HA, Fouque D, Soulage CO. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol. 2013 Jan;24(1):88-99.

p-Methylphenyl potassium sulfate是一种与慢性肾病进展、心血管风险和死亡率相关的原型蛋白质结合尿毒症毒素,来源于肝脏的酪氨酸和苯丙氨酸代谢产物[1,2]。p-Methylphenyl potassium sulfate的血清水平与肾功能衰竭的进展[3]、心血管风险和死亡率相关[4]。p-Methylphenyl potassium sulfate毒性机制包括促进炎症反应以及导致内皮功能障碍[5,6]

在体外,p-Methylphenyl potassium sulfate(0.05、0.125、0.25、0.5mM)处理原代成骨细胞24小时,通过激活c-Jun氨基末端激酶(JNK)和p38丝裂原活化蛋白激酶(p38 MAPK)通路,导致甲状旁腺激素1型受体(PTHR)下调,从而导致成骨细胞功能障碍[7]

在体内,p-Methylphenyl potassium sulfate(10mg/kg)腹腔注射给药于通过5/6肾切除诱发的慢性肾病(CKD)模型小鼠,每天给药两次连续治疗4周后,p-Methylphenyl potassium sulfate加重CKD小鼠的胰岛素抵抗,直接激活(细胞外信号调节激酶1/2)ERK1/2激酶,抑制胰岛素信号通路[8]

实验参考方法

Cell experiment [1]:

Cell lines

Primary osteoblastic cells

Preparation Method

Cell viability was evaluated using an MTT assay as described previously. Primary osteoblastic cells (1 × 103 cells/well) were inoculated into 96-well microplates. After culturing for 24h, various concentrations (0 to 0.5mM) of p-Methylphenyl potassium sulfate or indoxyl sulfate(IS)were added and the cells were incubated at 37 °C for 48 h. Then the cells were lysed with isopropanol/HCl solution, and the absorbance of each well was measured at 570nm with absorbance at 630nm as reference, using a microplate reader.

Reaction Conditions

0.05, 0.125, 0.25, 0.5mM; 24h

Applications

MTT assay revealed that p-Methylphenyl potassium sulfate at concentrations of 0.125mM and above significantly decreased the viability of primary osteoblasts, whereas IS decreased cell viability at 0.5mM but not at lower concentrations.

Animal experiment [2]:

Animal models

CD1 Swiss; C57BL/6J mice

Preparation Method

Moderate CKD was induced by 5/6 nephrectomy with a two-step surgical procedure. NaHCO3 (80mM) was added to the drinking water of CKD mice to prevent metabolic acidosis. CD1 Swiss mice were randomly assigned to receive twice daily (8:00 a.m. and 6:00 p.m.) intraperitoneal injections of p-Methylphenyl potassium sulfate (10mg/kg) or vehicle for control mice, sham mice, and CKD mice, for 4 weeks.

Dosage form

10mg/kg; twice a day for 4 weeks; i.p.

Applications

p-Methylphenyl potassium sulfate aggravates insulin resistance in CKD mice, directly activates (extracellular signal-regulated kinase 1/2) ERK1/2 kinase, and inhibits the insulin signaling pathway.

References:
[1]Tanaka H, Iwasaki Y, Yamato H, Mori Y, Komaba H, Watanabe H, Maruyama T, Fukagawa M. p-Cresyl sulfate induces osteoblast dysfunction through activating JNK and p38 MAPK pathways. Bone. 2013 Oct;56(2):347-54.
[2]Koppe L, Pillon NJ, Vella RE, Croze ML, Pelletier CC, Chambert S, Massy Z, Glorieux G, Vanholder R, Dugenet Y, Soula HA, Fouque D, Soulage CO. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol. 2013 Jan;24(1):88-99.

化学性质

Cas No. 91978-69-7 SDF
别名 对甲基硫酸钾; p-Tolyl sulfate potassium; p-Cresyl sulfate potassium
Canonical SMILES O=S(OC1=CC=C(C)C=C1)([O-])=O.[K+]
分子式 C7H7KO4S 分子量 226.29
溶解度 DMSO : ≥ 300 mg/mL (1325.73 mM) 储存条件 Store at -20°C
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1 mM 4.4191 mL 22.0955 mL 44.1911 mL
5 mM 0.8838 mL 4.4191 mL 8.8382 mL
10 mM 0.4419 mL 2.2096 mL 4.4191 mL
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