title: Simvastatin and artesunate impact the structural organization of adult Schistosoma mansoni in hypercholesterolemic mice.
abstract: Experimental data have shown that simvastatin and artesunate possess activity against Schistosoma mansoni worms in mice fed standard chow. However, little is known regarding the roles of these drugs in mice fed high-fat chow. We have extended past studies by measuring the effects of these drugs on the structural organization of adult schistosomes in hypercholesterolemic mice. For this purpose, mice were gavaged with either simvastatin or artesunate at nine weeks post-infection and were euthanized by cervical dislocation at two weeks post-treatment. Adult worms were then collected and examined by conventional light microscopy, morphometry and confocal laser scanning microscopy. Plasma total cholesterol and worm reduction rates were significantly increased in mice fed high-fat chow compared with their respective control groups. Simvastatin and artesunate caused changes in the tegument, tubercles, and reproductive system (testicular lobes, vitelline glands and ovarian cells), particularly when administered to mice fed high-fat chow. In particular, the tegument and tubercles were significantly thinner in artesunate-treated worms in mice fed high-fat chow compared with mice fed standard chow. This study thus demonstrated that simvastatin and artesunate have several novel effects on the structural organization of adult worms. Together, these results show, for the first time, that simvastatin and artesunate display antischistosomal activity in hypercholesterolemic mice.
authors.affiliation: Laboratory of Helminthology Romero Lascasas Porto, Department of Microbiology, Immunology and Parasitology, Faculty of Medical Sciences, Biomedical Center, State University of Rio de Janeiro, Brazil.
authors.forename: Alba Cristina Miranda de Barros
authors.initials: AC
authors.lastname: Alencar
authors.affiliation: Laboratory of Helminthology Romero Lascasas Porto, Department of Microbiology, Immunology and Parasitology, Faculty of Medical Sciences, Biomedical Center, State University of Rio de Janeiro, Brazil.
authors.forename: Thais da Silva
authors.initials: Tda S
authors.lastname: Santos
authors.affiliation: Laboratory of Helminthology Romero Lascasas Porto, Department of Microbiology, Immunology and Parasitology, Faculty of Medical Sciences, Biomedical Center, State University of Rio de Janeiro, Brazil.
authors.forename: Renata Heisler
authors.initials: RH
authors.lastname: Neves
authors.affiliation: Laboratory of Helminthology Romero Lascasas Porto, Department of Microbiology, Immunology and Parasitology, Faculty of Medical Sciences, Biomedical Center, State University of Rio de Janeiro, Brazil.
authors.forename: Eduardo José
authors.initials: EJ
authors.lastname: Lopes Torres
authors.affiliation: Lipid Laboratory, Faculty of Medical Science, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: José Firmino
authors.initials: JF
authors.lastname: Nogueira-Neto
authors.affiliation: Laboratory of Helminthology Romero Lascasas Porto, Department of Microbiology, Immunology and Parasitology, Faculty of Medical Sciences, Biomedical Center, State University of Rio de Janeiro, Brazil. Electronic address: machado@uerj.br.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Machado-Silva
mesh_terms: D000821:Animal Feed; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000648:ultrastructure; D012555:Schistosomiasis mansoni / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000871:Anthelmintics; D000924:Anticholesteremic Agents; D037621:Artemisinins; D004041:Dietary Fats; D000077332:Artesunate; D002784:Cholesterol; D019821:Simvastatin
keywords: Artesunate; Confocal laser microscopy; Hyperlipidemia; Scanning electron microscopy; Schistosoma mansoni; Simvastatin