MULTIFUNCTIONAL STIGMURIN I AND II FROM T. stigmurus SCORPION VENOM: THERAPEUTIC POTENTIAL IN EXPERIMENTAL SEPSIS MODEL
Scorpion venom; Tityus stigmurus; Antimicrobial peptides; sepsis.
Sepsis is a serious public health problem characterized by a severe infection-triggered systemic inflammation. The resistance of microorganisms to conventional antibiotics and the high mortality of sepsis have motivated the search for new therapeutic alternatives. Transcriptome analysis of T. stigmurus scorpion venom gland reported by our group demonstrated the presence of antimicrobial peptides with multifunctional activity, which may be used as templates for developing new anti-infective and/or anti-proliferative drugs. The aims of this study were to comparatively evaluate secondary structure, anti-proliferative effects and therapeutic potential of Stigmurin I and II, two antimicrobial peptides present in T. stigmurus venom. Circular dichroism analyses of Stigmurin II revealed environment-dependent changes similar to previously reported for Stigmurin I. Both peptides showed cytotoxic activity upon HepG2 cells and increased the cellular viability in murine macrophages in vitro. In murine sepsis model, they were able to reduced leucocyte migration and the number of bacterial cells in the peritoneal cavity after cecal ligation and puncture, as well as to inhibit the growth of microorganisms present in the fecal microbiota ex vivo. Taken together, these data indicate Stigmurin I and II as possible candidate molecules to be used in the treatment of sepsis.