Increase of the cytotoxic effect of Bothrops jararacussu venom on mouse extensor digitorum longus and soleus by potassium channel blockers and by Na(+)/K(+)-ATPase inhibition.
We investigated the myotoxicity of Bothrops jararacussu crude venom and other cytolytic agents on mouse isolated extensor digitorum longus (EDL) and soleus (SOL) muscles, which present distinct properties: EDL is a fast-twitch, white muscle with predominantly glycolytic fibers, while SOL is slow-twitch, red muscle with predominantly oxidative fibers. Muscles were exposed to B. jararacussu crude venom (25 microg/ml) and other crotaline venoms (Agkistrodon contortrix laticinctus; Crotalus viridis viridis; Crotalus durissus terrificus) at the same concentration. Basal creatine kinase (CK) release to bathing solution was 0.43+/-0.06 for EDL and 0.29+/-0.06 for SOL (U g(-)(1) h(-)(1), n=36 for each muscle). Sixty minutes after exposure to B. jararacussu venom, EDL presented higher increase in the rate of CK release than SOL, respectively, 13.2+/-1.5 and 2.9+/-0.7 U g(-)(1)h(-)(1), n=10-12. Muscle denervation, despite decreasing CK content, did not affect sensitivities to B. jararacussu venom. Ouabain and potassium channel blockers (TEA; clotrimazole; glibenclamide) increased the rate of CK release by B. jararacussu in EDL and SOL muscles, decreasing and almost abolishing the different sensitivity. When we exposed EDL or SOL muscles to Naja naja, Apis mellifera venoms (25 microg/ml), or Triton X-100 (0.01%), they showed similar rate of CK release. Our present data suggest that a mechanism involving intracellular calcium regulation or potassium channels may participate in the different sensitivity of EDL and SOL to B. jararacussu venom.
Tomaz
Marcelo A
MA
Departamento de Farmacologia Básica e Clínica, ICB, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.
Fernandes
Fabrício F A
FF
El-Kik
Camila Z
CZ
Moraes
Raphael A M
RA
Calil-Elias
Sabrina
S
Saturnino-Oliveira
Jeison
J
Martinez
Ana Maria B
AM
Ownby
Charlotte L
CL
Melo
Paulo A
PA
D000818:Animals; D017837:Bothrops; D003402:Creatine Kinase / Q000378:metabolism; D003435:Crotalid Venoms / Q000633:toxicity*; D066298:In Vitro Techniques; D051379:Mice; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000633:toxicity*; D015221:Potassium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D018675:Toxicity Tests
D003435:Crotalid Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010042:Ouabain; D003402:Creatine Kinase; D000254:Sodium-Potassium-Exchanging ATPase