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    Journal of Pharmacology and PharmacotherapeuticsNOW IN
    Article

    Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in a rat model

    José Sereno2★, Ana M. Romão2, Belmiro Parada2,3, Patrícia Lopes4, Eugénia Carvalho4, Frederico Teixeira2, Flávio Reis2★ Corresponding author

    1. 1Laboratory of Pharmacology and Experimental Therapeutics, IBILI, Medicine Faculty, Coimbra University.
    2. 2Department of Urology and Renal Transplantation, Coimbra University Hospital.
    3. 3Center for Neuroscience and Cell Biology, Coimbra, Portugal Research Paper.

    CORRESPONDENCE

    José Sereno

    Department of Urology and Renal Transplantation, Coimbra University Hospital.

    Volume 3, Issue 2 · pp. 143–148 · PUBLISHED 2012 · DOI: 10.4103/0976-500X.95513

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    Objective: To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation. Materials and Methods: The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation. Results: As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity. Conclusions: In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile.

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      Sereno, J., Romão, A. M., Parada, B., Lopes, P., Carvalho, E., Teixeira, F., & Reis, F. (2012). Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in a rat model. Journal of Pharmacology and Pharmacotherapeutics, 3(2), 143–148. https://doi.org/10.4103/0976-500X.95513