L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure

1 Internal Medicine, City Hospital, 45011 Adria; 2 Consiglio Nazionale delle Ricerche Institute of Neuroscience, Unit for Muscle Biology and Pathophysiology, Department of Biomedical Sciences, and 3 Department of Cardiovascular Pathology, University of Padua, 35100 Padua; 4 Department of Experimental Oncology, National Cancer Institute, 80072 Naples; 5 Scientific Department, Sigma Tau, 00040 Rome, Italy Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor- (TNF- ) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei. Proapoptotic agents, caspase-3 and -9, were increased, as well as serum levels of TNF- and its second messenger sphingosine. Treatment of rats with L -carnitine, known for its protective effect on muscle metabolism injuries, was found to inhibit caspases and to decrease the levels of TNF- and sphingosine, as well as the number of apoptotic myonuclei. Staurosporine was used in in vitro experiments to induce apoptosis in skeletal muscle cells in culture. When L -carnitine was applied to skeletal muscle cells, before staurosporine treatment, we observed a reduction in apoptosis. These findings show that L -carnitine can prevent apoptosis of skeletal muscles cells and has a role in the treatment of congestive heart failure-associated myopathy. tumor necrosis factor; sphingosine; caspases; staurosporine