In vitro evaluation of silver tungstate and analogues against Schistosoma mansoni

• Grant number: 24/14570-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 30, 2025
• End date: July 29, 2025
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Fernanda de Freitas Anibal
• Grantee: Mariana Carloni Anselmo
• Supervisor: Conor Caffrey
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 23/09844-9 - Evaluation of Silver Tungstate (±-Ag2WO4) in the control of murine schistosomiasis, BP.IC

Abstract

Schistosomiasis is a major global health concern, affecting millions of people worldwide. In Brazil, there are an estimated 6 to 8 million confirmed cases of Schistosoma mansoni infection. Praziquantel (PZQ) is the only drug recommended for the treatment of this parasitosis, according to the World Health Organization, but in view of some cases of ineffectiveness, it is essential to study new drugs capable of treating the infection. This study aims to evaluate the toxic effects of silver tungstate (AW-HRL) and its structural and functional analogs on the Naval Medical Research Institute (NMRI) strain of S. mansoni ex vivo, by assessing motility and mortality of adult worms using light microscopy, as well as the separation of mated couples. In addition, changes in the texture of the integument as well as alterations in the internal structures of the worm will be analyzed using transmission electron microscopy (TEM). The production of reactive oxygen species (ROS) will be assessed using the H2DCFDA technique on adult worms. The cytotoxic effects of the compounds on the host will be evaluated in vitro in human kidney cells (HEK293). Preliminary results show that AW-HRL presents comparable efficacy to PZQ in parasite load reduction, along with reducing egg production in infected mice. However, detailed mechanisms of how AW-HRL exerts activity in S. mansoni worms remains unknown. The additional compounds selected to be tested have previously been described as promising treatments or immunotherapies against schistosomiasis; they underwent testing for cytotoxicity on mice fibroblast cells (3T3), highlighting their potential uses. Therefore, in light of recent studies on the oxidative potential of these compounds, particularly silver tungstate, we intend to analyze the mechanism of action of AW-HRL in S. mansoni, comparing it with functional and structural analogues, in pursuit of more targeted and effective treatments for schistosomiasis.