Schepers Eva, Meert Natalie, Glorieux Griet, Goeman Jan, Van der Eycken Johan, Vanholder Raymond
Renal Division, Department of Internal Medicine, University Hospital, De Pintelaan 185, 9000 Gent, Belgium.
Nephrol Dial Transplant. 2007 Feb;22(2):592-6. doi: 10.1093/ndt/gfl584. Epub 2006 Oct 13.
Chronic renal insufficiency is associated with the retention of solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound uraemic retention solute, has been shown to exert toxic effects in vitro. Recently, however, it has been demonstrated that p-cresol in the human body is conjugated, with p-cresylsulphate as the main metabolite.
The present study evaluates the effect of p-cresylsulphate on the respiratory burst activity of leucocytes.
P-cresylsulphate significantly increased the percentage of leucocytes displaying oxidative burst activity at baseline. Oxidative burst activity of stimulated leucocytes was however not affected. In contrast, p-cresol had no effect on the leucocytes at baseline, but inhibited leucocytes burst activity after stimulation.
The present study demonstrates, for the first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a pro-inflammatory effect on unstimulated leucocytes. This effect could contribute to the propensity to vascular disease in the uraemic population.
慢性肾功能不全与通常由健康肾脏排出的溶质潴留有关。对甲酚是一种典型的与蛋白质结合的尿毒症潴留溶质,已被证明在体外具有毒性作用。然而,最近已证明人体中的对甲酚会发生共轭作用,以对甲酚硫酸盐作为主要代谢产物。
本研究评估对甲酚硫酸盐对白细胞呼吸爆发活性的影响。
对甲酚硫酸盐在基线时显著增加了显示氧化爆发活性的白细胞百分比。然而,刺激后白细胞的氧化爆发活性未受影响。相比之下,对甲酚在基线时对白细胞没有影响,但在刺激后会抑制白细胞的爆发活性。
本研究首次证明,对甲酚的主要体内代谢产物对甲酚硫酸盐对未刺激的白细胞具有促炎作用。这种作用可能导致尿毒症患者易患血管疾病。