Ac2-26 mimetic peptide inhibits local and systemic inflammatory process induced by Bothrops moojeni and the Lys-49-phospholipase A2 in a rat model

• Grant number: 15/12411-0
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: September 01, 2015 - February 29, 2016
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Sonia Maria Oliani
• Grantee: Sonia Maria Oliani
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 in the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) was evaluated using a peritonitis rat model. Peritonitis was induced by intraperitoneal injection of CV or its MjTX-II, a Lys-49 phospholipase A2, and after 15 minutes, rats were treated or not with Ac2-26. Control group received PBS. At 4 hours, CV and MjTX-II-induced peritonitis were characterized by neutrophilia (peritoneal exudate, blood and mesentery), and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours, the local inflammatory response was attenuated in the CV-induced peritonitis while MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment avoided neutrophil influx in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1² and IL-6 in the peritoneal exudates, which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with augmented number of macrophages and morphological alterations of juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of juxtamedullary structures, basal macrophage numbers and diminished AnxA1 levels in epithelial cells from distal tubules and renal capsules. Altogether our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes, indicating this peptide as a potential target for the development of new therapeutic strategies for the protection of snakebite envenomation. (AU)