Distinct effects of radicicol on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Abstract

This work aimed to investigate the influence of heat shock proteins (HSPs) on the myotoxic activity induced by the neurotoxin crotoxin (CTX), the major component of C.d. terrificus venom and the myotoxic sPLA2s, myotoxin II and myotoxin III (Mt II and Mt III respectively, isolated from Bothrops asper) in vivo and in vitro. Mice were treated with radicicol (0.05mg/20g b.w.), a HSP inductor, and received an intramuscular injection of CTX (0.085mg/kg b.w.), or Mt II (0.1 mg/kg b.w.), or Mt III (0.1 mg/kg b.w.) into the gastrocnemius muscle, however there was no protection against injury evaluated one day after toxin injection. Myofibers in culture were treated with 0.1 μM radicicol and exposed to CTX, or Mt II, or Mt III (133 ηg/μl, each). Membrane damage induced by CTX, Mt II and Mt III was assessed by cytochemistry using a fixable membrane wound marker (FITC-dx). It was observed that radicicol significantly reduced the percentage of damaged myofibers exposed to CTX (64%) and Mt III (53%). On the other hand, radicicol was less effective in reducing the number of damaged myofibers exposed to Mt II (25%). These preliminary results suggest that distinct intracellular pathways might be involved in myotoxicity induced by CTX and the Bothrops sp. PLA2 myotoxins. Financial support: FAPESP: 2009/53528-7