ABSTRACT
Snakebite envenomation is common in all inhabited continents of the world, with more than 100,000 fatalities occurring every year. Depending on the snake species involved, envenomation includes often disabling intense local tissue damage with inflammation, pain and myonecrosis, caused in part by molecules known as myotoxins. Myotoxins are found in the venoms of several snakes, and their homologs are also found in lizards and mammals (the Platypus). These small peptide toxins show a unique structural/physicochemical resemblance to β-defensins, which are anti-microbial peptides (AMPs) involved in the resistance of epithelial surfaces to microbial colonization. These similarities suggest a possible common phylogenetic and/or functional association among these myotoxic and anti-microbial peptides. These β-defensins seems to play a key role as toxins in the envenomation process by activating the immune system. Crotamine, purified from the venom of the South American Rattlesnake Crotalus durissus terrificus, is one of the first myotoxins to be characterized. In addition to its role in rapid prey incapacitation, several therapeutic applications of myotoxin a like peptides (mainly crotamine), for instance, as antitumor and anti-microbial agents, have been characterized and are listed in this chapter. The several different characterized biological activities exhibited by these myotoxin-like peptides are mostly dependent on their three-dimensional structure and positively charged surface (cationic feature). Herein, we present the main known myotoxins of venoms, introduce some alternatives for neutralizing their effects in snakebite envenomations, and discuss their mechanism of action(s), designated biological functions, and structural/functional similarities with AMPs (β-defensins). This chapter will therefore discuss the structure, biological activities and differences/similarities shared between the toxins with antitumoral/anti-microbial activities (namely, myotoxin-a and crotamine) and the immune effector (defensin-like) polypeptides. Interestingly, toxins and immune effectors share similar evolutionary and structural patterns, and they both seem to have evolved to defend against the threats of potential predators, microbial invasions and/or malignant cells.
