Abstract
5-aminolevulenic acid (ALA), an endogenous, non-proteinogenic, naturally occurring amino acid found in diverse organisms, is a precursor of heme biosynthesis. For apicomplexan protozoan parasites, an ALA and sodium ferrous citrate (SFC) combination was previously evaluated and suggested as a potential drug candidate for Plasmodium falciparum malaria. This study aimed to evaluate the potential of this combination against bovine babesiosis. ALA administration at 100 and 500 µM coupled with 10 µM SFC in culture medium significantly inhibited intraerythrocytic development and growth of Babesia bovis, which causes cerebral babesiosis in cattle, under in vitro culture. However, administration of 10 µM SFC only in the medium did not inhibit parasite growth. ALA/SFC was efficacious in treating babesiosis in an experimental animal model with B. microti, which causes debilitating babesiosis in mice. Female BALB/c mice were infected with B. microti and administered a single oral dose of ALA/SFC combination daily in different concentrations for 30 days. Treatment with ALA/SFC at 4/0.4 mg/kg body weight significantly suppressed parasite development in the mice blood circulation and resulted in significantly lower parasitemia. Moreover, body weight loss in the mice has been improved significantly compared with the control group at the peak of parasitemia. Treated mice showed moderate decreases in red blood cell count, hemoglobin value, and hematocrit compared with those observed in the control group, indicating an effect in moderating progressive anemia. These findings suggested the potential of ALA/SFC to achieve symptomatic improvement against bovine babesiosis.
Highlights
Babesiosis is a tick-borne disease caused by intraerythrocytic protozoan parasites of the genus Babesia
Babesia bovis infection causes a severe disease characterized by hemolytic anemia and high mortality in adult bovines [1], whereas B. microti invades and replicates in red blood cells (RBCs) of animals, including humans, to cause zoonotic babesiosis [2]
The apicoplast, which is involved in the heme biosynthesis pathway of malaria parasites, is essential for parasite development [7], and Aminolevulenic acid (ALA) was suggested to be a potential antimalarial drug that targets the heme biosynthesis pathway in this organelle [10]
Summary
Babesiosis is a tick-borne disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Babesia bovis infection causes a severe disease characterized by hemolytic anemia and high mortality in adult bovines [1], whereas B. microti invades and replicates in red blood cells (RBCs) of animals, including humans, to cause zoonotic babesiosis [2]. Infection of B. microti in mouse has been used as an experimental infection model to evaluate the effect of potential compounds for the treatment of bovine babesiosis [3,4]. The control strategies currently applied for bovine babesiosis include treatment of the infected animal, tick control using acaricide and live attenuated vaccine administration, in which emerging resistance to drugs and acaricides and lack of effective vaccines are the main obstacles [1,5]. Most apicomplexan parasites have a non-photosynthetic plastid called the apicoplast, which is involved in some
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