Original Paper Acta Haematol 2004;112:184–188 DOI: 10.1159/000081269 Cyclosporin A-Associated Changes in Red Blood Cell Membrane Composition, Deformability, Blood and Plasma Viscosity in Rats Evin Ademoglu a Sule Tamer b Isil Albeniz c Cahide Gokkusu a Sevda Tanrikulu a Departments of a Biochemistry, b Physiology and c Biophysics, Istanbul Faculty of Medicine, University of Istanbul, Istanbul, Turkey Received: March 25, 2003 Accepted after revision: March 23, 2004 Dr. Evin Ademoglu Department of Biochemistry Istanbul Faculty of Medicine, University of Istanbul TR–34093 Capa Istanbul (Turkey) Tel. +90 212 414 21 89, ext. 124, Fax +90 212 414 22 53, E-Mail evin@istanbul.edu.tr ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2004 S. Karger AG, Basel 0001–5792/04/1124–0184$21.00/0 Accessible online at: www.karger.com/aha Key Words Blood viscosity W Cyclosporin A W Membrane lipids W Plasma viscosity W Red blood cell deformability Abstract Most of the studies concerning the effects of cyclosporin A (Cs A) on red blood cell (RBC) rheology were carried out in human transplant recipients who may still have residual insufficiency and concomitant administration of other immunosuppressive and antihypertensive drugs. The aim of this study is to evaluate the effects of Cs A on red cell rheology and membrane composition in non- transplant healthy rats. Female Wistar albino rats were divided into two groups of 10 animals each. Rats re- ceived 10 mg/kg Cs A, i.p. or saline for 4 weeks. Cs A administration significantly increased the RBC deforma- bility, and plasma and blood viscosity (p ! 0.001, p ! 0.01 and p ! 0.01, respectively). Cs A administration to the rats increased RBC membrane cholesterol (CHO) levels and the CHO/phospholipid (PL) ratio significantly (p ! 0.01 and p ! 0.05, respectively) but did not change RBC membrane proteins and membrane PL levels. These results suggest that Cs A changes the rheological func- tions of RBC and lipid content of RBC membrane in healthy rats and thereby it may play an important role in the regulation of microcirculation. Copyright © 2004 S. Karger AG, Basel Introduction Cyclosporin A (Cs A) is a potent immunosuppressive agent used in transplant surgery and in the treatment of various autoimmune diseases because of its specific in- hibiting effect on signal transduction pathways of T cell receptor through the formation of a Cs A-cyclophilin com- plex [1]. The major immunosuppressive activities of Cs A are directed at blocking interleukin-2 (IL-2) synthesis [2, 3]. Decreased IL-2 synthesis leads to reduced T cell acti- vation or prolonged periods of T cell unresponsiveness [4] and thus inhibits organ rejections. Although Cs A is the most commonly used immunosuppressive agent in the transplant therapy in addition to several other diseases, its clinical use is limited by its adverse side effects such as hepatotoxicity, nephrotoxicity, hypertension, microvas- cular thrombosis, hyperlipidemia and cancer [5–8]. Alterations in microcirculation include reduction of capillary blood flow, viscosity alterations and distur- bances of red blood cell (RBC) and white blood cell (WBC) rheology [9]. It has been acknowledged that red cell rheology has a considerable clinical significance in many disorders including diabetes mellitus, sepsis, ath- erosclerosis, hypertension and intrauterine growth retar- dation [10–16]. It has also been demonstrated that Cs A therapy may modify the RBC rheology [17–20]. Most of the studies concerning the effects of Cs A on RBC rheolo-