title: Differential effects of diethylcarbamazine, tetracycline and the combination on Brugia pahangi adult females in vitro.
abstract: Anti-filarial effects of diethylcarbamazine (DEC), tetracycline (TC) and the combination on Brugia pahangi adult females were studied in 7-day cell-free culture, in terms of microfilaria release, parasite motility, MTT assay for parasite viability and embryogram. TC 50 microg/ml (TC50) effectively reduced microfilaria release from day 1 of culture. Combined with DEC 100 microg/ml (DEC100) or DEC 500 microg/ml (DEC500), microfilaria release reduced further and synergistically. TC50 also reduced motility, but DEC100 and DEC500 did not. The combination of TC50 and DEC500 reduced motility synergistically. The MTT assay supported the results of motility study in general. The embryogram showed that only DEC500 reduced the total number of intrauterine embryos, especially ova, indicating that DEC500 inhibited early embryogenesis. TC50 did not affect the total number of embryos, but resulted in apparent accumulation of microfilariae in the uterus, suggesting that the drug inhibited release of microfilariae in this in vitro system. These results clarified different anti-female mechanisms between DEC and TC. A PCR-based study showed that endosymbiont bacteria, Wolbachia, in B. pahangi females decreased significantly after TC treatment. However, this study could not determine whether the effects of TC were direct or Wolbachia-mediated.
authors.affiliation: Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto-machi, Nagasaki 852-8523, Japan.
authors.forename: Nipul Kithsiri
authors.initials: NK
authors.lastname: Gunawardena
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujimaki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Aoki
authors.forename: Noriko
authors.initials: N
authors.lastname: Mishima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ezaki
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Uni
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017179:Brugia pahangi / Q000187:drug effects* / Q000196:embryology / Q000382:microbiology / Q000502:physiology; D003470:Culture Media; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D005369:Filaricides / Q000008:administration & dosage / Q000494:pharmacology*; D008842:Microfilariae / Q000187:drug effects / Q000382:microbiology; D021261:Parasitic Sensitivity Tests; D013559:Symbiosis; D013752:Tetracycline / Q000008:administration & dosage / Q000494:pharmacology*; D020577:Wolbachia / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D005369:Filaricides; D013752:Tetracycline; D004049:Diethylcarbamazine