Effect of thalidomide on the skeletal muscle in experimental heart failure.
BACKGROUND
Tumour Necrosis Factor alpha (TNFalpha) has been shown to contribute to heart failure (CHF) progression.


OBJECTIVE
We have tried to antagonise the detrimental effects of TNFalpha on skeletal muscle apoptosis, by using thalidomide, a drug that inhibits its biosynthesis.


METHODS
CHF was induced in 20 rats by injecting monocrotaline, which determines right ventricle (RV) failure. After 2 weeks, when CHF developed, 12 rats were treated with thalidomide 3.5.mg/kg per day for 2 weeks. Eight had saline and served as CHF controls.


RESULTS
Thalidomide failed to decrease TNFalpha and its second messenger sphingosine (SPH), but was able to prevent the shift toward the fast myosin heavy chains. In the Tibialis Anterior muscle of the thalidomide group, the degree of atrophy, the number of apoptotic nuclei and the levels of caspases, were similar to those of the CHF controls.


CONCLUSIONS
Thalidomide, at the doses used in this study, which are the same employed for the treatment of tubercolosis, leprosy, AIDS and cancer in humans, did not lower either TNFalpha or SPH and only marginally influenced the apoptosis-induced muscle atrophy. Since other TNFalpha blockers are under investigation for improving the clinical status of patients with CHF, the present data could be relevant in the design of randomised clinical trials in humans.
Vescovo
Giorgio
G
Internal Medicine, Adria Hospital, Italy. ldl@civ.bio.unipd.it
Ravara
Barbara
B
Angelini
Annalisa
A
Sandri
Marco
M
Carraro
Ugo
U
Ceconi
Claudio
C
Dalla Libera
Luciano
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced / Q000473:pathology*; D016686:Monocrotaline / Q000633:toxicity; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000037:antagonists & inhibitors / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000473:pathology
D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D016686:Monocrotaline; D018995:Myosin Heavy Chains; D013110:Sphingosine