Characterization of mechanism(s) molecular(s) involved in myotoxic effect of crotamine, a toxin from the venom of rattlesnake with potential teranostic employment

• Grant number: 15/08812-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Mirian Akemi Furuie Hayashi
• Grantee: Lucas de Carvalho Porta
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The various biological activities presented by crotamine have been studied for a long time, although little is known about the mechanism(s) involved in molecular action(s) of your myotoxic effect, which is characterized by skeletal muscle immobilization when injected into rodents and which stimulated their identification and characterization in rattlesnake venom. Initially it was suggested that this effect was due to blocking action on the sodium channels. However, it was subsequently demonstrated that crotamine is not able to act directly on these ion channels.Its action on potassium channels have been suggested and studied subsequently, however, without demonstration of its correlation with myotoxic effect. Pilot studies in vivo, recently carried out by the group, point to the possibility of crotamine action not only peripherally, but also with central effects involved in the immobilization of the hind legs of rodents. When performing simultaneous injection of crotamine and antipsychotic thioridazine in mice, it was observed potentiation effect of both myotoxic crotamine as the sedative effect of thioridazine. Thus, it is suggested here that these two compounds can present a common molecular activity, and relevant to the eventual identification of the main molecular target of crotamine in rodents. Therefore, it is expected in this study better understand the mechanisms that lead to the myotoxic effect exploring the effect observed for the crotamine in the presence of the antipsychotic.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAMPEIRO, JOANA D.; MARINOVIC, MARCELO P.; CARAPETO, FERNANDO CINTRA; DAL MAS, CAROLINE; MONTE, GABRIELA GUILHERME; PORTA, LUCAS CARVALHO; NERING, MARCELA B.; OLIVEIRA, EDUARDO B.; HAYASHI, MIRIAN A. F.. Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile. Amino Acids, v. 50, n. 2, p. 267-278, FEB 2018. (15/08812-0, 13/13392-4, 17/02413-1)