Evaluation of 5-Aminolevulenic Acid Plus Ferrous Ion for Its Potential to Improve Symptoms of Bovine Babesiosis

A. Elata, K. Suganuma, Ehab Mossaad, I. Zafar, E. Galon, Keiichiro Yoshimoto, Tohru Tanaka, X. Xuenan, S. Kawazu
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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.
5-氨基乙酰丙酸加铁离子改善牛巴贝斯症症状的潜力评价
5-氨基乙酰丙酸(ALA)是一种内源性、非蛋白原性、天然存在于各种生物体中的氨基酸,是血红素生物合成的前体。对于顶端复合体原生动物寄生虫,ALA和柠檬酸亚铁钠(SFC)的组合先前被评估为恶性疟原虫疟疾的潜在候选药物。本研究旨在评估这种组合对抗牛巴贝斯虫病的潜力。在体外培养条件下,在培养基中以100和500µM的ALA与10µM的SFC联合给药显著抑制了牛巴贝虫的红细胞内发育和生长,这会导致牛脑巴贝虫病。然而,仅在培养基中施用10µM SFC并不能抑制寄生虫的生长。ALA/SFC在用B.microti建立的实验动物模型中有效治疗巴贝斯虫病,这种疾病会导致小鼠衰弱性巴贝斯虫症。用B.microti感染雌性BALB/c小鼠,并每天以不同浓度单次口服ALA/SFC组合,持续30天。用4/0.4mg/kg体重的ALA/SFC治疗显著抑制了小鼠血液循环中的寄生虫发育,并导致寄生虫血症显著降低。此外,在寄生虫血症高峰期,与对照组相比,小鼠的体重减轻情况得到了显著改善。与对照组相比,治疗后的小鼠红细胞计数、血红蛋白值和红细胞压积略有下降,表明其在缓解进行性贫血方面有作用。这些发现表明ALA/SFC有可能改善牛巴贝斯虫病的症状。
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