Radicicol improves regeneration of skeletal muscle previously damaged by crotoxin in mice.
This work investigates the influence of heat shock proteins (HSPs) on necrosis and subsequent skeletal muscle regeneration induced by crotoxin (CTX), the major component of Crotalus durissus terrificus venom. Mice were treated with radicicol, a HSP inductor, followed by an intramuscular injection of CTX into the gastrocnemius muscle. Treated groups were sacrificed 1, 10 and 21 days after CTX injection. Muscle histological sections were stained with toluidine blue and assayed for acid phosphatase or immunostained with either neuronal cell adhesion molecule (NCAM) or neonatal myosin heavy chain (MHCn). Muscle samples were also submitted to Western blotting analysis. The results show that CTX alone and CTX combined with radicicol induced a similar degree of myofiber necrosis. CTX-injured muscles treated with radicicol had increased cross-sectional areas at 10 and 21 days post-lesion compared with untreated CTX-injured muscles. Additionally, radicicol significantly increased the number of NCAM-positive satellite cells in the gastrocnemius at one day post-CTX injury. CTX-injured muscles treated with radicicol contained more MHCn-positive regenerating myofibers compared with untreated CTX-injured muscles. These results suggest that HSPs contribute to the regeneration of myofibers damaged by CTX. Additionally, further studies should investigate the potential therapeutic effects of radicicol in skeletal muscles affected by Crotalus venom.
Conte
T C
TC
Department of Anatomy, Biomedical Sciences Institute, University of São Paulo, Av. Lineu Prestes 2415, 05508-900 São Paulo, SP, Brazil.
Franco
D V
DV
Baptista
I L
IL
Bueno
C R
CR
Selistre-de-Araújo
H S
HS
Brum
P C
PC
Moriscot
A S
AS
Miyabara
E H
EH
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003439:Crotoxin / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D012038:Regeneration / Q000187:drug effects*
D000935:Antifungal Agents; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018942:Macrolides; D019006:Neural Cell Adhesion Molecules; D003439:Crotoxin; C035359:monorden