Table of Contents
ISRN Pharmacology
Volume 2013, Article ID 605640, 9 pages
http://dx.doi.org/10.1155/2013/605640
Research Article

On the Performance of Trimetazidine and Vitamin E as Pharmacoprotection Agents in Cyclosporin A-Induced Toxicity

1Clinical Biochemistry III, Instituto de Bioquímica Clínica, Facultad de Bioquímica Química y Farmacia, Universidad Nacional de Tucumán, Balcarce 747, Tucumán, 4000 San Miguel de Tucumán, Argentina
2Instituto de Bioquímica Clínica, Facultad de Bioquímica Química y Farmacia, Universidad Nacional de Tucumán, Balcarce 747, Tucumán, 4000 San Miguel de Tucumán, Argentina

Received 26 December 2012; Accepted 17 January 2013

Academic Editors: G. M. Campo, G. Edwards, and B.-N. Wu

Copyright © 2013 De la Cruz Rodríguez Lilia Cristina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The immunosuppressant drug cyclosporin A (CyA) has been used in diseases with immunological basis and in transplant patients. Nephrotoxicity and hepatotoxicity are the main adverse effects of this drug. To find a protective drug against those effects we assayed the cardioprotector Trimetazidine (TMZ) and vitamin E, used as nutritional supplements to alleviate oxidative stress. Six groups of eight male Wistar rats each were prepared (groups A–F): A, control; B, vitamin E (10 mg/Kg/day); C, TMZ (20 mg/Kg/day); D, 25 mg/Kg/day CyA; E, CyA and vitamin E (25 mg/Kg/day CyA + 10 mg/Kg/day Vit E); F, TMZ for 20 days (20 mg/kg/day); and then CyA (25 mg/kg/day) and TMZ (20 mg/Kg/day). The experiment lasted 120 days. The exposure of rats to CyA promoted nephrotoxicity and hepatotoxicity with an increase in serum urea, creatinine, and glutamate dehydrogenase (GLDH). Structural and ultrastructural studies of liver and kidney were performed. Group D showed adverse effects induced by CyA since statistically significant differences were found with respect to the control group (A). Vitamin E (E) showed no protective effect. Pretreatment with TMZ (F) attenuated the adverse effects of CyA. We conclude that CyA-induced nephrotoxicity and hepatotoxicity are attenuated by the cytoprotective effect of TMZ. TMZ inhibits the reabsorption and, consequently, the accumulation of CyA in the cell. The antioxidant capacity of vitamin E did not improve the effect of CyA.