The role of the H2S donor, ATB-346, in the evolution of experimental sepsis

• Grant number: 17/03211-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Ana Laura Volpi Martins
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Sepsis, a condition of considerable clinical relevance, in view of its high mortality rates and the high costs demanded, is characterized as a systemic inflammatory response secondary to an infection. It was described an impairment in neutrophil migration to the infection site during sepsis - which are important agents to contain the pathogen to the initial infection site and to eliminate it. Subsequently, it was demonstrated that the desensibilization of CXCR2 is one of the mechanisms involved in this impairment and that the treatment with NaHS, a H2S donor, in an experimental model, contributed to the decrease of this process, resulting in a significant improvement in animals survival rates. Moreover, a recently developed drug, ATB-346 - which consists in a H2S donor coupled to Naproxen -, was described as an inflammation attenuator. Therefore, in view of the beneficial effect described to H2S in sepsis and to ATB-346 in inflammation control, this project has as main aim to evaluate the effect of ATB-346 treatment in cecal ligation and puncture (CLP) sepsis experimental model. (AU)