Cardiovascular Pharmacology Bemiparin improves the total antioxidant status in plasma José García-de-la-Asunción a, ⁎, Paula de Toro a , Verónica Planelles a , Javier Belda a , Jaime Perez-Griera b , Juan Gambini c , Elena Domenech c a Department of Anesthesiology and Critical Care, Hospital Clínico Universitario de Valencia, Valencia, Spain b Laboratory of Biochemistry, Hospital Clínico Universitario de Valencia, Valencia, Spain c Department of Physiology, University of Valencia, Valencia, Spain abstract article info Article history: Received 20 August 2008 Received in revised form 11 November 2008 Accepted 24 November 2008 Available online 3 December 2008 Keywords: Low molecular weight heparin Bemiparin Plasma antioxidant status Oxidative stress markers The aim of this work is to test the protective effect of bemiparin (3500 I.U., s.c.) against oxidative stress in plasma from healthy volunteers. We have evaluated the total antioxidant activity in plasma, superoxide dismutase and glutathione peroxidase activities, and oxidized glutathione and malondialdehyde levels, in two groups: treated (n =20) and control (n =15). Blood samples were collected at: basal, 2, 4, 6, 8 and 10 h. Total antioxidant activity and antioxidant enzymes activity were higher in the treated group at 2–6 h. However, oxidized glutathione and malondialdehyde levels were lower in the treated group at same times. The results suggest that bemiparin exerts an early beneficial effect against oxidative stress in plasma. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Low molecular weight heparins are antithrombotic drugs, widely used in all hospitalized patients, for the prevention or treatment of deep venous thrombosis. Low molecular weight heparins are obtained by either chemical or enzymatic depolymerization from unfractio- nated heparin. Compared to unfractionated heparin, low molecular weight heparins have a reduced risk of bleeding, greater bioavail- ability at low doses and a longer half life (Green et al., 1994). Bemiparin sodium is a new second generation low molecular weight heparin, with a high anti-Xa/anti-IIa ratio (Frydman, 1996). In earlier works, some authors found that the administration of low molecular weight heparin protected against oxidative stress and histological abnormalities in adriamycin-induced glomerulopathy (Deepa and Varalakshmi, 2003a), in calcium oxalate-induced oxida- tive renal injury (Rajeswari and Varalakshmi, 2006), and in oxidative injury caused by adriamycin-induced cardiac and hepatic toxicity (Deepa and Varalakshmi, 2003b). Moreover, a favourable influence of low molecular weight heparin has been found in mitigating the peroxidation of erythrocyte membrane and in rising the activities of the antioxidant enzymes (superoxide dismutase, catalase and glu- tathione peroxidase) in oxidative damage induced by adriamycin and an atherogenic diet (Deepa and Varalakshmi, 2003c). Also, some works reported that low molecular weight heparin normalized lipid peroxidation levels and antioxidant enzymatic defences in aorta, heart, liver and kidney of rats fed with an atherogenic diet (Deepa and Varalakshmi, 2003d, 2005). Recently, a work reported that low molecular weight heparin decreased the oxidative stress in hemodia- lysis patients, whereas unfractionated heparin increased the oxidative stress and inflammation (Poyrazoglu et al., 2006). The aim of this study was to test the potential antioxidant effect of bemiparin sodium on levels of oxidative stress markers, superoxide dismutase and glutathione peroxidase activities and total antioxidant activity in plasma from healthy volunteers. 2. Materials and methods 2.1. Healthy volunteers We enrolled 35 young healthy volunteers (19 females and 16 males) aged 25–44 years (control: 29.8 ± 9.0 years, treated: 30.5 ± 8.2 years) from Hospital Clínico Universitario, Valencia, Spain. The Ethic Committee of our hospital approved the protocol and informed consent was obtained from each volunteer. The volunteers followed a standard diet during the day before the initiation of fasting (3 h before and during blood samples collection), with water ad libitum. The volunteers were randomly assigned to receive bemiparin (n = 20) or a sodium chloride solution 0.9 g/dl (n =15). Bemiparin was administered subcutaneously at a single dosage of 3.500 I.U. (Hibor ® ) immediately after the baseline time. Blood samples were collected by venipuncture at the following times: basal, 2, 4, 6, 8 and 10 h. After blood samples were centrifuged at 1750 g for 12 min. Plasma was separated and stored at - 80 °C until analysis. European Journal of Pharmacology 602 (2009) 380–382 ⁎ Corresponding author. Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario de Valencia, Av. Blasco Ibañez 17, 46010-Valencia, Spain. Tel.: +34 96 3862653; fax: +34 96 3987831. E-mail address: jgdelaasuncion@hotmail.com (J. García-de-la-Asunción). 0014-2999/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2008.11.042 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar