Cyclosporin A attenuates skeletal muscle damage induced by crotoxin in rats.
This work was undertaken to determine the role of the calcineurin pathway on the necrosis of skeletal muscle induced by crotoxin, the major component of the venom of Crotalus durissus terrificus. Rats were treated with cyclosporin A (CsA), a calcineurin inhibitor, for 5 days and, in the 6th day, received an intramuscular injection of crotoxin into the tibialis anterior muscle. Rats were also treated with diclofenac, a non-steroidal anti-inflammatory drug, for 5 days and, on the 6th day, injected with crotoxin. All treated groups were sacrificed 24 h after injection of crotoxin. Tibialis anterior and soleus muscles were removed, frozen and stored in liquid nitrogen. Histological sections were stained with Toluidine Blue and assayed for acid phosphatase. The results show that CsA, but not diclofenac, is able to significantly minimize myonecrosis promoted by crotoxin. In conclusion, CsA attenuates skeletal muscle necrosis induced by crotoxin, indicating that the calcineurin pathway is essential for crotoxin myotoxic activity. The myoprotective effect of CsA is not related to its anti-inflammatory effect since diclofenac, a cyclo-oxygenase inhibitor, was not able to produce myoprotection.
Miyabara
E H
EH
Departments of Histology/Embriology, Biomedical Sciences Institute, Av Lineu Prestes 1524, ICBI, University of São Paulo, São Paulo, SP, Brazil.
Tostes
R C
RC
Selistre de Araújo
H S
HS
Aoki
M S
MS
Salvini
T F
TF
Moriscot
A S
AS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D003439:Crotoxin / Q000633:toxicity*; D016572:Cyclosporine / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D004008:Diclofenac; D016572:Cyclosporine; D003439:Crotoxin