P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production.
BACKGROUND
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.


METHODS
The present study evaluates the effect of p-cresylsulphate on the respiratory burst activity of leucocytes.


RESULTS
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.


CONCLUSIONS
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.
Schepers
Eva
E
Renal Division, Department of Internal Medicine, University Hospital, De Pintelaan 185, 9000 Gent, Belgium.
Meert
Natalie
N
Glorieux
Griet
G
Goeman
Jan
J
Van der Eycken
Johan
J
Vanholder
Raymond
R
D015415:Biomarkers / Q000097:blood; D003408:Cresols / Q000378:metabolism* / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D014511:Uremia / Q000097:blood*
D015415:Biomarkers; D003408:Cresols; D004731:Endotoxins; D005609:Free Radicals; D013463:Sulfuric Acid Esters; C032538:4-cresol; C408690:4-cresol sulfate