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- Title
Cost-effective In Vivo and In Vitro Mouse Models for Evaluating Anticryptosporidial Drug Efficacy: Assessing Vorinostat, Docetaxel, and Baicalein.
- Authors
Liu, Mingxiao; Zhang, Di; Wang, Dongqiang; Wu, Xiaodong; Zhang, Ying; Yin, Jigang; Zhu, Guan
- Abstract
Background Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. Methods Cryptosporidium tyzzeri , a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis , was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. Results Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. Conclusions Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.
- Subjects
CRYPTOSPORIDIUM; DRUG efficacy; DOCETAXEL; LABORATORY mice; ANIMAL disease models; CRYPTOSPORIDIUM parvum
- Publication
Journal of Infectious Diseases, 2023, Vol 228, Issue 10, p1430
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiad243