Cyclosporine (CyA) is an immunosuppressive agent used after solid organ transplantation, but its clinical use is limited by side effects, the most important of which is nephrotoxicity. In a previous work we demonstrated that (L)-propionylcarnitine (L-PC) a propionyl ester Of (L)-carnitine, is able to prevent CyA-induced acute nephrotoxicity reducing lipid peroxidation in the isolated and perfused rat kidney. CyA administration was associated with a dose dependent increase in renovascular resistance prevented by a pretreatment with L-PC. The aim of the present study was to confirm L-PC protective effect, previously described in vitro, in an in vivo rat model. Chronic nephrotoxicity study was carried out for 28 days. L-PC was administered (i.p. 25 mg/kg b.w.) since the first day, while CyA treatment was performed for the last 21 days (by oral administration 25 mg/k,g b.w.). We demonstrate that L-PC was able to significantly lower blood pressure in CyA treated animals and to prevent CyA induced decrease in creatinine clearance. Moreover renal tissue analysis revealed that L-PC was able to reduce lipid hydroperoxide content and morphological abnormalities associated to chronic CyA administration. In conclusion our study demonstrated for the first time in vivo that L-PC protects against functional and tissue damage associated to chronic CyA administration. (c) 2006 Elsevier SAS. All rights reserved.
|Autori:||ORIGLIA N; MIGLIORI M; PANICHI V; FILIPPI C; BERTELLI A; CARPI A; GIOVANNINI L|
|Titolo:||Protective effect of L-propionylcarnitine in chronic cyclosporine-a induced nephrotoxicity|
|Anno del prodotto:||2006|
|Digital Object Identifier (DOI):||10.1016/j.biopha.2005.06.014|
|Appare nelle tipologie:||1.1 Articolo in rivista|