2. Academic Validation
  3. Promising efficacy of nitrogen-containing bisphosphonates against the infection of Cryptosporidium spp

Promising efficacy of nitrogen-containing bisphosphonates against the infection of Cryptosporidium spp

  • Int J Parasitol Drugs Drug Resist. 2025 Aug 6:29:100607. doi: 10.1016/j.ijpddr.2025.100607.
Wenyan Hou 1,  Xinyi Chen 1,  Yingying Zhang 1,  Longfei Wu 1,  Songying Sun 1,  Jiaye Guo 1,  Wenchao Zhao 1,  Junqiang Li 1,  Sumei Zhang 2,  Longxian Zhang 3,  Xiaoying Li 4
Affiliations

Affiliations

  • 1 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450056, China; International Joint Research Laboratory for Zoonotic Diseases of Henan, Zhengzhou, 450046, Henan, China; Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China.
  • 2 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450056, China; International Joint Research Laboratory for Zoonotic Diseases of Henan, Zhengzhou, 450046, Henan, China; Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. Electronic address: smzhang2815@henau.edu.cn.
  • 3 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450056, China; International Joint Research Laboratory for Zoonotic Diseases of Henan, Zhengzhou, 450046, Henan, China; Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. Electronic address: zhanglx8999@henau.edu.cn.
  • 4 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450056, China; International Joint Research Laboratory for Zoonotic Diseases of Henan, Zhengzhou, 450046, Henan, China; Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. Electronic address: lixiaoying@henau.edu.cn.
PMID: 40782657 DOI: 10.1016/j.ijpddr.2025.100607
Abstract

Cryptosporidiosis is a major diarrheal disease that affects both humans and Animals. Fully effective drug for treating cryptosporidiosis is still lacking. Nitrogen-containing bisphosphonates have been reported to inhibit Cryptosporidium growth in vitro; however, the in vivo efficacy against Cryptosporidium remain unevaluated. This study determined the anti-Cryptosporidium effect of three nitrogen-containing bisphosphonates risedronate, ibandronate, and zoledronate through both in vitro and in vivo experiments. It was determined that risedronate exhibited the highest therapeutic index of 39.10 among the three compounds, with the median effective concentration low to 17.44 μM against Cryptosporidium parvum Infection in vitro. In vivo experiments showed that the high dose (10 mg/kg/d) of risedronate and ibandronate significantly reduced the shedding of Cryptosporidium tyzzeri oocyst, with no toxicity in ICR mice. Histopathological examinations of ICR mice indicated that high and medium (2 mg/kg/d) doses of the bisphosphonates could reduce intestinal damage, recover the height of intestinal villi and crypt depth, led to more intact intestinal structures, and risedronate showed the most promising effects. Furthermore, the three compounds modulated the elevated levels of IL-2, IL-4, and TNF-α cytokines, induced by C. tyzzeri Infection, towards normalcy in a dose-dependent manner. In conclusion, the efficacy of three nitrogen-containing bisphosphonates against the in vitro and in vivo Infection of Cryptosporidium spp. was assessed. Risedronate show promising effect for further development of new anticryptosporidial drugs.

Keywords

Cryptosporidiosis; Cryptosporidium spp.; In vivo assessment; Nitrogen-containing bisphosphonates.

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