title: Establishment of a novel model of onychomycosis in rabbits for evaluation of antifungal agents.
abstract: We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents.
authors.affiliation: R&D Laboratories, Pola Pharma Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812, Japan. t-shimamura@pola-pharma.co.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kubota
authors.forename: Saori
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Taku
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Mukai
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077768:Ciclopirox; D007764:Lacquer; D008297:Male; D008954:Models, Biological; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use; D014009:Onychomycosis / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits; D014249:Trichophyton / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D000935:Antifungal Agents; D009025:Morpholines; D011728:Pyridones; D000077768:Ciclopirox; C038974:amorolfine