Effect of sulfated polysaccharides such as fucosylated chondroitin sulfate and an analogue of heparin in preventing severe malaria

• Grant number: 11/02290-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2011
• End date: April 30, 2013
• 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

Abstract

Malaria is undoubtedly the most important parasitic disease infecting the world each year 300-500 million individuals. Although most cases does not lead to death, 1-3 million infections progress to the complicated forms of the disease (severe malaria) such as; cerebral malaria (CM) and pregnancy associated malaria (PAM). Besides the process of parasite cytoadherence, individuals with CM or PAM have an imbalance of the immune response, resulting in increased expression of proinflammatory cytokines. Sulfated polysaccharides such as heparin, condrotin sulfate A (CSA) or dextran sulfate have been tested in the prevention and treatment of severe malaria, in view of the ability of these compounds to inhibit the cytoadherence of infected erythrocytes (IEs) to endothelial receptors. However, the use of mammalian origin of these compounds has been discouraged, because they present a potential risk of carrying harmful contaminants to human health and some of them also present a high bleeding potential. The analogue of heparin, extracted from the bivalve Nodipecten nodosus (HS-Mollusk), and the fucosylated chondroitin sulfate (FucCS), extracted from sea cucumber Luwigothurea grisea, present similar structure with the commercial heparin and anticoagulant properties, but without significant hemorrhagic effect. Furthermore, studies indicate that these compounds can inhibit thrombus formation and the expression of P-selectin and L-selectin, preventing the proinflammatory. Thus, it opens perspectives for using FucCS and HS-Mollusk in the treatment of severe malaria, including the process of parasite adhesion to endothelial receptors. (AU)