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Toxins 2017, 9(7), 229; doi:10.3390/toxins9070229

The Uremic Toxin Indoxyl Sulfate Accelerates Thrombotic Response after Vascular Injury in Animal Models

1
Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
2
Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
3
Department of Physical Chemistry, Medical University of Bialystok, Mickiewicza 2A Str., 15-222 Bialystok, Poland
4
Department of Pharmacology and Toxicology, University of Warmia and Mazury, Al. Warszawska 30, 10-082 Olsztyn, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: R. Vanholder
Received: 1 June 2017 / Revised: 16 July 2017 / Accepted: 17 July 2017 / Published: 19 July 2017
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
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Abstract

Chronic kidney disease (CKD) patients are at high risk for thrombotic events. Indoxyl sulfate (IS) is one of the most potent uremic toxins that accumulates during CKD. Even though IS is associated with an increased risk for cardiovascular disease, its impact on thrombotic events still remains not fully understood. The purpose of the study was to evaluate the direct effect of IS on thrombotic process. We examined the impact of acute exposure to IS on thrombus development induced by electric current in Wistar rats, intravital thrombus formation after laser-induced injury in the mice endothelium, coagulation profile, clot formation dynamics, platelet aggregations, and erythrocyte osmotic resistance. IS doses: 10, 30 and 100 mg/kg body weight (b.w.) increased weight of thrombus induced by electric current in dose-dependent manner (p < 0.001). Furthermore, two highest IS doses increased laser-induced thrombus formation observed via confocal system (increase in fluorescence intensity and total thrombus area (p < 0.01)). Only the highest IS dose decreased clotting time (p < 0.01) and increased maximum clot firmness (p < 0.05). IS did not affect blood morphology parameters and erythrocyte osmotic resistance, but augmented collagen-induced aggregation. Obtained data indicate that IS creates prothrombotic state and contributes to more stable thrombus formation. Thus, we concluded that IS may be one of crucial uremic factors promoting thrombotic events in CKD patients. View Full-Text
Keywords: indoxyl sulfate; uremic toxin; thrombosis; hemostatic disorder; chronic kidney disease; prothrombotic state; cardiovascular event; tryptophan derivative indoxyl sulfate; uremic toxin; thrombosis; hemostatic disorder; chronic kidney disease; prothrombotic state; cardiovascular event; tryptophan derivative
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Karbowska, M.; Kaminski, T.W.; Marcinczyk, N.; Misztal, T.; Rusak, T.; Smyk, L.; Pawlak, D. The Uremic Toxin Indoxyl Sulfate Accelerates Thrombotic Response after Vascular Injury in Animal Models. Toxins 2017, 9, 229.

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