In vitro killing of Babesia bovis by the ornithine analog alpha-monofluoromethyldehydroornithine methyl ester.
The effects of the 2 ornithine decarboxylase inhibitors alpha-difluoromethylornithine (DFMO) and alpha-monofluoromethyldehydroornithine methyl ester (delta MFMO-ME) on growth of Babesia bovis blood stages in vitro were tested. The DFMO had no apparent effects on in vitro growth of B. bovis nor on the morphology of the parasite at concentrations up to 20 mM. In contrast, delta MFMO-ME had cytotoxic effects on B. bovis at 0.5 mM which were more pronounced at 5 mM. delta MFMO-ME caused both a decrease in percentage parasitized erythrocytes and a degeneration of parasites after 12 h exposure, and the magnitude of both effects was dose-dependent. The effects of delta MFMO-ME were not reversible for B. bovis precultured for 12 h (5 mM) or 24 h (0.5 mM) in drug before culturing the parasite in drug-free medium. Unexpectedly, 300 microM putrescine did not reverse the effects of delta MFMO-ME on B. bovis blood stage, raising the possibility that inhibition of ornithine decarboxylase is not responsible for these effects.
Jasmer
D P
DP
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
Goff
W L
WL
D000818:Animals; D001403:Babesia / Q000187:drug effects*; D002417:Cattle; D000518:Eflornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000494:pharmacology
D065108:Ornithine Decarboxylase Inhibitors; C047399:2-(fluoromethyl)dehydroornithine methyl ester; D011700:Putrescine; D000518:Eflornithine