title: In Vitro and in Vivo Effects of Nitrofurantoin on Experimental Toxoplasmosis.
abstract: Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.
authors.affiliation: Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, Iksan 54538, Korea.
authors.forename: Seon-Ju
authors.initials: SJ
authors.lastname: Yeo
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133002, PR China.
authors.forename: ChunMei
authors.initials: C
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 54538, Korea.
authors.forename: SungYeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, Iksan 54538, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D045744:Cell Line, Tumor; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000469:parasitology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009582:Nitrofurantoin / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects; D014122:Toxoplasma / Q000187:drug effects*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D008315:Malondialdehyde; D009582:Nitrofurantoin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
keywords: HeLa cell; Toxoplasma gondii; mouse; nitrofurantoin; selectivity; therapeutic efficacy