Abstract
Apicidin, a histone deacetylase inhibitor, has a broad spectrum of anti-protozoal activities against apicomplexan parasites. In the present study, we evaluated the inhibitory effect of apicidin on the asexual growth of bovine Babesia parasites (B. bovis and B. bigemina) in vitro, as well as on the in vivo growth of B. microti in mice. The growth of B. bovis and B. bigemina was significantly inhibited in the presence of 3 ng/ml apicidin. Complete inhibition of B. bovis and B. bigemina growth was achieved on the fourth and third days, respectively, after treatment with 729 ng/ml apicidin. These parasites failed to grow again even when drug-free medium was substituted. The 50% inhibitory concentrations of apicidin against B. bovis and B. bigemina were determined as 7.1 and 20.7 ng/ml, respectively, in in vitro cultures with serum-containing M199 medium. Severe morphological signs of damage, such as pyknotic and degenerative changes, were observed in the treated parasites. Apicidin 2 mg/kg caused significant inhibition of B. microti growth and altered the parasitemia dynamics in mice, compared with untreated control mice. Apicidin could be an effective chemotherapeutic agent for the treatment of bovine and human babesioses.
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