Effect of Tityus serrulatus venom in mice genetically selected for high or low acute inflammatory response

• Grant number: 11/09555-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2011
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Mônica Spadafora Ferreira
• Grantee: Mônica Spadafora Ferreira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Fernanda Calheta Vieira Portaro ; Nancy Starobinas ; Orlando Garcia Ribeiro Filho ; Osvaldo Augusto Brazil Esteves Sant'Anna

Abstract

Scorpionism has increased in recent years, according to the Ministry of Health, and the Tityus serrulatus species causes the most serious accidents in Brazil. Several toxins active on ion channels have been described and some enzymatic activities were detected in different species of scorpions. The neurotoxic effects caused by the venom of T. serrulatus (VTs) can be explained largely by the toxins that act on ion channels. However, proteases and enzymatic activators may also be involved in the inflammation and pulmonary edema induced by the venom. It was shown that VTs is able to induce a systemic inflammatory response causing the release of acute phase proteins and inflammatory cytokines in patients and experimental animals. Previous data from our group showed that VTs and some components with proteolytic activity, induced in vitro, the production of proinflammatory cytokines such as IL-6, IFNg and TNF±, as well as chemokines by murine splenocytes. It was shown recently that mice genetically selected for high inflammatory response (AIRmax) have higher cellular influx and inflammatory mediators production in response to the venom of Bothrops jararaca, compared to the line selected for low inflammatory response (AIRmin), suggesting that genetic factors are involved the inflammatory response to snake venom. This study aims to evaluate the effects of VTs and some isolated compounds in AIRmax and AIRmin strains of mice. We will evaluate the histopathological changes, cell populations, adhesion molecules, cytokines and chemokines present in the lung and peripheral blood of animals treated with the venom and some isolated components. The study of the action of VTs in these lines aims to determine whether genetic factors are involved in the response to scorpion venom and thereby contribute to better understanding of the mechanisms involved in the poisoning. (AU)