In vitro and in vivo efficacy of aurintricarboxylic acid against Neospora caninum infection.

Abstract

Bovine neosporosis, a protozoal disease caused by Neospora caninum ( N. caninum), poses a significant threat to the global cattle industry, resulting in substantial economic losses that are difficult to quantify. The current lack of effective commercial vaccines and specific treatments highlights the urgent need for the development of potent drugs against N. caninum. In this study, we investigate the efficacy of aurintricarboxylic acid (ATA), a derivative of polyaromatic carboxylic acid, against N. caninum both in vitro and in vivo. Cell cytotoxicity is evaluated using CCK-8 kits. N. caninum proliferation within cells is assessed by qPCR analysis. Transmission electron microscopy (TEM) is employed to examine the ultrastructures of N. caninum tachyzoites. The efficacy of ATA against N. caninum infection is validated in a mouse model. Our findings indicate that ATA not only inhibits N. caninum proliferation but also reduces parasite loads within individual cells. Furthermore, ATA (20 and 40 μM) has immunomodulatory effects by downregulating the mRNA expressions of N . caninum-induced cytokines, including tumor necrosis factor-α (TNF-α), interferon (IFN-α, -β, and -γ), and β-defensin 5 (BNBD5). ATA treatment directly targets and eliminates N. caninum by disrupting its ultrastructure. The in vivo study confirms the potential of ATA to increase body weight, decrease parasite loads in the lungs and duodenum, and ameliorate the pathological effects induced by N . caninum infection in mice. In conclusion, this study represents the first evidence of the anti- N. caninum ability of ATA and provides compelling data to support its potential as a candidate for developing anti- N. caninum drugs.