Subacute toxicity of crotoxin upon the skeletal muscle of mice: morphological and biochemical studies

• Grant number: 16/15732-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Marcia Gallacci
• Grantee: Marcela Carneiro de Oliveira
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Crotoxin (CTX), the major component of Crotalus durissus terrificus (South American rattlesnake) snake venom is a potent myotoxic neurotoxin that promotes both pre- and postsynaptic blockage of neuromuscular transmission and rhabdomyolysis. However, despite its toxicity, CTX has potential therapeutic value due to its immunomodulatory, anti-inflammatory, antimicrobial, anti-tumor and anti-nociceptive activities. Thus, the development of pre-clinical studies in order to characterize the subacute toxicity of CTX is necessary. In this sense, considering that the neuromuscular junction is the main target of the toxic action of CTX, this project aims to assess the consequences of subacute administration tolerable doses of CTX on the structure and function of the skeletal muscle of mice. To achieve these goals will be used an association of morphological approaches, such as optical, electron and confocal microscopy and the biochemical dosage of creatine kinase. Thus, in addition to providing the characterization and understanding of the side and adverse effects of subacute administration of CTX, this study will also contribute to increase the knowledge about pathophysiological processes of the skeletal muscle (myonecrosis/regeneration and local and systemic myonecrosis) using the CTX as a pharmacological tool.