Toxocara canis: search for a potential drug amongst beta-carboline alkaloids--in vitro and mouse studies.
The goal of this study was to search for new treatments for Toxocara canis using both in vitro and in vivo experiments. We specifically looked for a treatment for T. canis larva migrans, and examined beta-carboline alkaloids (17 compounds) with various structural modifications, both in in vitro and in vivo experiments. In the in vitro experiments, screening for nematocidal activity on the T. canis second stage larvae, cytotoxic activity, and immune activity in the host were undertaken. Compound 17 was selected, as it exhibited nematocidal activity for T. canis larvae and did not have any cytotoxic or immunosuppressive activity in the host. The effectiveness of compound 17 was then examined using T. canis larvae infected mice in in vivo experiments. To evaluate the anthelmintic effect, the relative mobility value for the larvae was examined in addition to the number of larvae in the brain, skeletal muscle, and liver. Compound 17 was also examined in both free and liposome-entrapped (LE) forms. Polyethylene glycol (PEG)-LE compound 17 showed an anthelmintic effect in which the number of larvae in the brain was decreased compared free albendazole. PEG-LE compound 17 also effectively suppressed the mobility of the larva in brain and skeletal muscle. The experimental procedure employed assisted in the discovery of this potential candidate and is a promising approach for finding alternative therapeutic regimens for T. canis larva migrans.
Satou
Tadaaki
T
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. satou@phar.toho-u.ac.jp
Horiuchi
Akiko
A
Akao
Nobuaki
N
Koike
Kazuo
K
Fujita
Koichiro
K
Nikaido
Tamotsu
T
D000470:Alkaloids / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002243:Carbolines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004283:Dog Diseases / Q000188:drug therapy / Q000469:parasitology; D004285:Dogs; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007814:Larva / Q000187:drug effects; D007815:Larva Migrans / Q000188:drug therapy*; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D017166:Toxocara canis / Q000187:drug effects*; D014120:Toxocariasis / Q000188:drug therapy / Q000469:parasitology
D000470:Alkaloids; D002243:Carbolines; D008081:Liposomes; D009569:Nitric Oxide