对甲酚硫酸盐是一种主要的尿毒症毒素,来源于酪氨酸和苯丙氨酸的代谢产物通过肝脏,存在于慢性肾脏病 (CKD) 患者的血液中。
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The p-Cresol is a protein-bound uremic retention solute 1.
Free p-Cresol was found to be a cardiovascular risk factor in non-diabetic hemodialysis patients. In patients with diabetes, the level of both free p-cresol and total p-cresol were markedly higher. In patients treated by hemodialysis, the levels of these two forms of p-cresol were also significantly higher than that of patients treated by hemodiafiltration. The univariate cox proportional hazard analysis showed that the concentration of free p-cresol was obviously associated with cardiovascular disease (CVD). Quite many patients with high free p-cresol concentrations had new fatal or non-fatal cardiovascular events. Besides that, p-cresol was also found to inhibit cell proliferation. It inhibited the proliferation of cultured endothelial cells by 26% without affecting cell viability. Moreover, p-cresol treatment reduced endothelial wound repair by 19%, 28% and 40% at concentrations of 10, 25 and 50 μg/ml, respectively 1,2.
参考文献:
1.?Meijers B K I, Bammens B, De Moor B, et al. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney international, 2008, 73(10): 1174-1180.
2.?Dou L, Bertrand E, Cerini C, et al. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney international, 2004, 65(2): 442-451.
对甲酚是一种与蛋白质结合的尿毒症滞留溶质1。
游离对甲酚被发现是非糖尿病血液透析患者的心血管危险因素。在糖尿病患者中,游离对甲酚和总对甲酚的水平明显更高。在接受血液透析治疗的患者中,这两种形式的对甲酚水平也明显高于接受血液透析滤过治疗的患者。单变量cox比例风险分析显示游离对甲酚浓度与心血管疾病(CVD)明显相关。许多游离对甲酚浓度高的患者发生了新的致命或非致命心血管事件。除此之外,还发现对甲酚可抑制细胞增殖。它抑制培养的内皮细胞增殖 26%,而不影响细胞活力。此外,浓度为 10、25 和 50 μg/ml 的对甲酚治疗分别使内皮伤口修复减少了 19%、28% 和 40% 1,2。
Cell experiment [1]: | |
Cell lines |
Human umbilical vein endothelial cells |
Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
24 h |
Applications |
Without and with HSA, 10 mug/mL, 25 mug/mL and 50 mug/mL p-cresol induce a decrease in endothelial cell proliferation by 21%, 38% and 54%, respectively. Without HSA, endothelial wound repair in monolayers treated with p-cresol is prominently lower than in cells treated with control medium. 10 mug/mL, 25 mug/mL and 50 mug/mL p-cresol reduce endothelial wound repair by 19%, 28% and 40%, respectively. With HSA, only 50 mug/mL p-cresol prominently blocks endothelial wound repair. |
Animal experiment [2]: | |
Animal models |
Rat |
Dosage form |
Intravenously injection of p-cresol (10 mg/kg) in rats with normal and decreased renal function |
Preparation method |
Dissolved in isotonic saline |
Applications |
P-cresol was injected in mice with normal and decreased renal function, and compared the results with those obtained for creatinine (60 mg/kg) under similar conditions. In rats with decreased renal function, p-cresol serum concentration displays a minimal decline, in contrast to rats with normal renal function. In rats with normal renal function, 21.0±10.0% of the injected p-cresol was excreted in urine. In rats with renal failure, the amount is 6.7±7.5%. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
参考文献: 1. Dou L, Bertrand E, Cerini C, et al. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney international, 2004, 65(2): 442-451. 2. Lesaffer G, De Smet R, D'Heuvaert T et al. Comparative kinetics of the uremic toxin p-cresol versus creatinine in rats with and without renal failure. Kidney Int. 2003 Oct; 64(4):1365-73. |
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