Brief Research Report ARTICLE
Clofazimine, but not isoniazid or rifampicin, augments platelet activation in vitro
- 1Department of Immunology, University of Pretoria, South Africa
- 2Department of Internal Medicine, Centre of Excellence in Mathematical and Statistical Sciences, University of the Witwatersrand, South Africa
Although the inclusion of clofazimine in the chemotherapeutic regimens of patients with multidrug-resistant (MDR) tuberculosis (TB) has contributed to improved outcomes, concerns remain about the cardiotoxic potential of this agent. Accordingly, the current study was undertaken with the primary objective of investigating the effects of clofazimine on the reactivity of human platelets in vitro as a possible, seemingly unexplored, mechanism of cardiotoxicity.Platelet-rich plasma (PRP) prepared from the blood of healthy, adult humans was treated with clofazimine (0.625-10 mg/L), or the primary anti-TB agents, isoniazid and rifampicin (final concentrations of 5 and 10 mg/L for each), followed by addition of either adenosine 5-diphosphate (ADP) or thrombin and measurement of platelet activation according to the magnitude of expression of CD62P (P-selectin) using flow cytometry. Clofazimine, but neither isoniazid nor rifampicin, caused dose-related potentiation of both ADP- and thrombin-activated expression of CD62P by platelets, achieving statistical significance at threshold concentrations of 0.625 and 2.5 mg/L respectively. These stimulatory effects of clofazimine on platelet activation were partly attenuated by pre-treatment of PRP with the membrane-stabilising agent, α-tocopherol. Clofazimine, at concentrations within the therapeutic range, augments platelet activation in vitro, probably by a mechanism linked to membrane destabilisation, which, if operative in vivo, may exacerbate the risk of TB-associated cardiovascular disease.
Keywords: adenosine 5'-diphosphate, Isoniazid, Neutrophils, rifampicin, Thrombin, Clofazimine, platelets, P-selectin (CD62P)
Received: 25 Sep 2018;
Accepted: 30 Oct 2018.
Edited by:Mohamed M. Abdel-Daim, Suez Canal University, Egypt
Reviewed by:Marta C. Monteiro, Universidade Federal do Pará, Brazil
Essa M. Saied, Humboldt-Universität zu Berlin, Germany
Mohamed Elbadawy, Benha University, Egypt
Copyright: © 2018 ANDERSON, Theron, Nel, Durandt, Cholo, Feldman and Tintinger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. RONALD ANDERSON, University of Pretoria, Department of Immunology, Pretoria, South Africa, email@example.com