Protective effect of L-propionylcarnitine in chronic cyclosporine-a induced nephrotoxicity.
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/kg 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.
Origlia
Nicola
N
Department of Neuroscience, Pharmacology section, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
Migliori
Massimiliano
M
Panichi
Vincenzo
V
Filippi
Cristina
C
Bertelli
Aldo
A
Carpi
Angelo
A
Giovannini
Luca
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; C003223:propionylcarnitine; D016572:Cyclosporine; D003404:Creatinine; D002331:Carnitine