Inhibitory effects of pepstatin A and mefloquine on the growth of Babesia parasites.
We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan. muugii_f@yahoo.com
Tserendorj
T
Munkhjargal
Mahmoud
M
AbouLaila
Mohamad Alaa
MA
Terkawi
Thillaiampalam
T
Sivakumar
Madoka
M
Ichikawa
Batdorj
B
Davaasuren
Tserendorj
T
Nyamjargal
Naoaki
N
Yokoyama
Ikuo
I
Igarashi
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001403:Babesia / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D041001:Babesia microti / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D001404:Babesiosis / Q000188:drug therapy* / Q000469:parasitology; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005260:Female; D020128:Inhibitory Concentration 50; D015767:Mefloquine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests / Q000379:methods; D010436:Pepstatins / Q000008:administration & dosage / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
D010436:Pepstatins; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D015767:Mefloquine; C031375:pepstatin