Mechanism of action of Lipoxin in the Protection Against Experimental Cerebral Malaria

• Grant number: 16/13805-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2016
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: Fabio Trindade Maranhão Costa
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Julio Cesar Soares Aliberti

Abstract

Malaria is the most widespread parasitic disease, and despite the many efforts made to eradicate malaria, it accounts for more than half million deaths per year because the host-parasite interactions are not completely understood yet. Cerebral malaria (CM) is a severe neurological complication of infection with Plasmodium falciparum. Even after the appropriate antimalarial treatment, fatality rates range from 10 to 20% which highlights the importance of understanding the pathogenesis of this disease and of implementing new, rapidly acting interventions in combination with anti-plasmodium treatment. Although, cerebral malaria pathogenesis is complex and incompletely understood, observations from animal models and P. falciparum-infected humans support a hypothesis that it involves sequestration of parasitized erythrocytes and leukocytes by the brain microvasculature, and production of pro-inflammatory cytokines, such as IFN-³, TNF-±, lymphotoxin-± e IL-12. However, the use of single knockout mutants for several pro-inflammatory cytokines have failed to show an obvious influence on cerebral malaria pathogenesis, suggesting that redundancy among those mediators. Previous results demonstrate that lipoxins, a class of anti-inflammatory lipid mediator derived from lipoxygenase-mediated metabolism of arachidonic acid, limit host damage during experimental cerebral malaria (ECM). In addition, animals treated with lipoxin showed prolonged survival and diminished brain inflammation. Thus, in the search for efficient therapies against CM and a better understanding of the disease pathogenesis, the aim of this project is to elucidate the mechanisms involved in the lipoxin-induced CM protection and to determine its potential use, as adjuvant therapy, in association with antimalarials to treat severe malaria. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MOTTIN, MELINA; BORBA, JOYCE V. V. B.; BRAGA, RODOLPHO C.; TORRES, PEDRO H. M.; MARTINI, MATHEUS C.; PROENCA-MODENA, JOSE LUIZ; JUDICE, CARLA C.; COSTA, FABIO T. M.; EKINS, SEAN; PERRYMAN, ALEXANDER L.; et al. The A-Z of Zika drug discovery. DRUG DISCOVERY TODAY, v. 23, n. 11, p. 1833-1847, NOV 2018. (12/16525-2, 16/00194-8, 17/02353-9, 16/13805-5)