Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP
E H MiyabaraA S Moriscot

Abstract

Previous studies have shown that calcineurin activity plays a critical role in the myotoxic activity induced by crotoxin (CTX), a group II phospholipase A(2) (PLA(2)) with neurotoxic and myotoxic actions. In order to address whether calcineurin is also important for the activity of non-neurotoxic group II PLA(2) myotoxins we have compared the effects of calcineurin inhibition on the myotoxic capacity of CTX and the non-neurotoxic PLA(2)s, myotoxin II (Mt II) and myotoxin III (Mt III) from Bothrops asper venom. Rats were treated with cyclosporin A (CsA) or FK506, calcineurin inhibitors, and received an intramuscular injection of either CTX, Mt II or Mt III into the tibialis anterior. Animals were killed 24 h after injection of toxins. Tibialis anterior was removed and stored in liquid nitrogen. Myofibers in culture were also treated with CsA or FK506 and exposed to CTX, Mt II and Mt III. It was observed that, in contrast to CTX, CsA and FK506 do not attenuate myotoxic effects induced by both Mt II and Mt III in vivo and in vitro. The results of the present study suggest that calcineurin is not essential for the myotoxic activity of Mt II and Mt III, indicating that distinct intracellular pathways might be involved in myonecrosis...Continue Reading

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Citations

Mar 1, 2012·PLoS Neglected Tropical Diseases·Irene ZornettaCesare Montecucco
Jun 25, 2008·Toxicon : Official Journal of the International Society on Toxinology·T C ConteE H Miyabara
Oct 5, 2007·Toxicon : Official Journal of the International Society on Toxinology·José María GutiérrezBruno Lomonte
Jun 15, 2011·Journal of Biochemical and Molecular Toxicology·Jonas Golart da SilvaAlexandra Acco
Jul 9, 2013·Toxicon : Official Journal of the International Society on Toxinology·Anita MalhotraRoger S Thorpe

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