Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study.
Propionyl-L-carnitine (PLC) has been shown to exert beneficial effects in experimental models of peripheral arterial diseases, such as ergotamine-induced tail gangrene and bilateral femoral arteries occlusion in rats. These models, however, present some drawbacks. The present study was performed to determine whether repeated oral administration of PLC improves the functional, histologic, and metabolic parameters in rats with long-lasting chemically induced peripheral arteriopathy. Peripheral arteriopathy was induced by injecting Na laurate in both the femoral arteries of rats. The walking capacity of the animals (treadmill test) was evaluated at different times and up to 5 weeks after Na laurate injection. Histological examination of vessels and muscles was performed at the end of the experimental period (5 weeks). In separate experiments the level of high-energy phosphates was determined with 31P NMR methodology in the leg muscles. Injection of Na laurate impaired (p < 0.05) the walking capacity of rats, caused thickening of the intima and marked narrowing of the vasal lumen, and reduced the ATP and PCr levels in muscles by 42% and 25%, respectively. PLC given orally for 7 days at 30, 60, 120, and 250 mg/kg dose-dependently decreased the severity of walking capacity impairment by 19%, 41%, 64%, and 71%, respectively. Long-term administration (4 weeks) of PLC (60 and 250 mg/kg os) caused a significant improvement of walking capacity throughout the entire period. The improvement persisted 1 week after discontinuation of the treatment. The severity of the vascular and muscular damages was markedly reduced, particularly in animals treated with the highest dose. Alterations in ATP and PCr levels were significantly (p < 0.05) diminished by PLC (120 mg/kg os) administered daily for 15 days starting 24 hours after Na laurate injection, or for 11 days starting 4 days after Na laurate. The dextro-isomer of the compound was completely inactive, and L-carnitine improved motor performance to a much lesser degree than an identical dose of PLC. It is suggested that the activity of PLC is linked to its metabolic effects on fatty acid oxidation, with consequent preservation of high-energy phosphate levels.
Corsico
N
N
Sigma-Tau S.p.A., Pomezia, Rome, Italy.
Nardone
A
A
Lucreziotti
M R
MR
Spagnoli
L G
LG
Pesce
D
D
Aureli
T
T
Di Cocco
M E
ME
Miccheli
A
A
Conti
F
F
Arrigoni Martelli
E
E
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002331:Carnitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006614:Hindlimb; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine