Evaluation of the in vitro growth-inhibitory effect of epoxomicin on Babesia parasites.
Epoxomicin potently and irreversibly inhibits the catalytic activity of proteasomal subunits. Treatment of proliferating cells with epoxomicin results in cell death through accumulation of ubiquinated proteins. Thus, epoxomicin has been proposed as a potential anti-cancer drug. In the present study, the inhibitory effects of epoxomicin on the in vitro growth of bovine and equine Babesia parasites were evaluated. The inhibitory effect of epoxomicin on the in vivo growth of Babesia microti was also assessed. The in vitro growth of five Babesia species that were tested was significantly inhibited (P<0.05) by nanomolar concentrations of epoxomicin (IC(50) values=21.4+/-0.2, 4+/-0.1, 39.5+/-0.1, 9.7+/-0.3, and 21.1+/-0.1nM for Babesia bovis, Babesia bigemina, Babesia ovata, Babesia caballi, and Babesia equi, respectively). Epoxomicin IC(50) values for Babesia parasites were low when compared with diminazene aceturate and tetracycline hydrochloride. Combinations of epoxomicin with diminazene aceturate synergistically potentiated its inhibitory effects in vitro on B. bovis, B. bigemina, and B. caballi. In B. microti-infected mice, epoxomicin caused significant (P<0.05) inhibition of the growth of B. microti at the non-toxic doses of 0.05 and 0.5mg/kg BW relative to control groups. Therefore, epoxomicin might be used for treatment of babesiosis.
Aboulaila
Mahmoud
M
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
Nakamura
Kazuya
K
Govind
Yadav
Y
Yokoyama
Naoaki
N
Igarashi
Ikuo
I
D000818:Animals; D001403:Babesia / Q000254:growth & development*; D001404:Babesiosis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D001681:Biological Assay; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000469:parasitology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy / Q000469:parasitology*; D006736:Horses; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D014709:Vero Cells
D004791:Enzyme Inhibitors; D009842:Oligopeptides; C078846:epoxomicin