title: In vitro and in vivo safety and efficacy studies of amphotericin B on Babesia gibsoni.
abstract: Babesia gibsoni is a causative pathogen of canine babesiosis, which is commonly treated with anti-babesial drugs; however, the development of novel, more effective anti-babesial drugs is necessary because the currently used drugs cannot remove the parasites from dogs. Therefore we investigated the anti-babesial effect of amphotericin B (AmB), a membrane-active polyene macrolide antibiotic. The interaction of such compounds with sterols in bilayer cell membranes can lead to cell damage and ultimately cell lysis. AmB exhibits in vitro activity against B. gibsoni in normal canine erythrocytes within 12h. We also studied liposomal AmB (L-AmB), a liposomal formulation of AmB that required a longer incubation period to reduce the number of parasites. However, L-AmB completely inhibited the invasion of free parasites into erythrocytes. These results indicated that free parasites failed to invade erythrocytes in the presence of L-AmB. Both AmB and L-AmB induced mild hemolysis of erythrocytes. Moreover, the methemoglobin level and the turbidity index of erythrocytes were significantly increased when erythrocytes were incubated with AmB, suggesting that AmB induced oxidative damage in erythrocytes. Finally, the anti-babesial activity of AmB in vivo was observed. When experimentally B. gibsoni-infected dogs were administered 0.5 and 1mg/kg AmB by the intravenous route, the number of parasites decreased; however, recurrence of parasitemia was observed, indicating that AmB did not eliminate parasites completely. Blood urea nitrogen and creatinine of dogs were abnormally elevated after the administration of 1mg/kg AmB. These results indicate that AmB has in vivo activity against B. gibsoni; however, it does not eliminate parasites from infected dogs and affects kidney function at a high dose.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: masayama@vetmed.hokudai.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Harada
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Sue Yee
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Ohsuga
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001403:Babesia / Q000187:drug effects*; D001404:Babesiosis / Q000188:drug therapy* / Q000469:parasitology; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D008297:Male; D018512:Parasitemia / Q000662:veterinary
chemical_list: D000900:Anti-Bacterial Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: Amphotericin B; Anti-babesial drug; Babesia gibsoni; Liposomal amphotericin B