title: Antiparasitic activity of menadione (vitamin K3) against Schistosoma mansoni in BABL/c mice.
abstract: Schistosomiasis is one of the neglected tropical diseases affecting nearly quarter of a billion people in economically challenged tropical and subtropical countries of the world. Praziquantel (PZQ) is the only drug currently available to treat this parasitic disease in spite being ineffective against juvenile worms and concerns about developing resistance to treat reinfections. Our earlier in vitro viability studies demonstrated significant antiparasitic activity of menadione (MEN) (vitamin K3) against Schistosoma mansoni adult worms. To gain insight into plausible mechanism of antischistosomal activity of MEN, its effect on superoxide anion levels in adult worms were studied in vitro which showed significant increases in both female and male worms. Further confirmation of the deleterious morphological changes in their teguments and organelles were obtained by ultrastructural analysis. Genotoxic and cytotoxic studies in male Swiss mice indicated that MEN was well tolerated at the oral dose of 500mg/kg using the criteria of MNPCE frequency and PCE/RBC ratio in the bone marrow of infected animals. The in vivo antiparasitic activity of MEN was conducted in female BALB/c mice infected with S. mansoni and significant reductions (P<0.001) in total worm burden were observed at single oral doses of 40 and 400mg/kg (48.57 and 61.90%, respectively). Additionally, MEN significantly reduced (P<0.001) the number of eggs in the liver of infected mice by 53.57 and 58.76%, respectively. Similarly, histological analysis of the livers showed a significant reduction (P<0.001) in the diameter of the granulomas. Since MEN is already in use globally as an over-the-counter drug for a variety of common ailments and a dietary supplement with a safety record in par with similar products when used in recommended doses, the above antiparasitic results which compare reasonably well with PZQ, make a compelling case for considering MEN to treat S. mansoni infection in humans.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA.
authors.forename: Govind J
authors.initials: GJ
authors.lastname: Kapadia
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Ingrid A O
authors.initials: IAO
authors.lastname: Soares
authors.affiliation: Global Biotechnology Resource Center, 145 Rosewood Drive, Streamwood, IL 60107, USA.
authors.forename: G Subba
authors.initials: GS
authors.lastname: Rao
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Badoco
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Furtado
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Mariana B
authors.initials: MB
authors.lastname: Correa
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Tavares
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil.
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Cunha
authors.affiliation: Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, Brazil. Electronic address: lizandra.magalhaes@unifran.edu.br.
authors.forename: Lizandra G
authors.initials: LG
authors.lastname: Magalhães
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006099:Granuloma / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000648:ultrastructure; D012552:Schistosomiasis / Q000188:drug therapy; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D000977:Antiparasitic Agents; D024483:Vitamin K 3
keywords: Menadione; Naphthoquinone; Schistosoma mansoni; Vitamin K(3)