Laboratoire de Parasitologie-Mycologie, Rouen University Hospital and EA7510, University of Rouen, Rouen, France.
Laboratoire d'Anatomo-Pathologie, Rouen University Hospital, Rouen, France.
Parasitology. 2021 Jul;148(8):975-984. doi: 10.1017/S0031182021000524. Epub 2021 Mar 29.
Cryptosporidiosis is a gastrointestinal illness with profuse diarrhoea. Although there are no other Food and Drug Administration (FDA)-approved alternatives for the treatment of cryptosporidiosis, nitazoxanide (NTZ) can be qualified as partially effective. In immunosuppressed conditions, severe and/or disseminated cryptosporidiosis may occur and patients should be treated parenterally. To achieve the goal of developing parenteral treatment for cryptosporidiosis, the current study was undertaken to investigate the in vitro and in vivo anticryptosporidial activity of aminoxanide. This new l-tert-leucyl thiazolide is a soluble prodrug of tizoxanide (TIZ), the main metabolite of NTZ. Confirming the good efficacy of aminoxanide in Cryptosporidium parvum-infected HCT-8 cells with a 50% inhibitory concentration of 1.55 μm (±0.21), in immunosuppressed C. parvum-infected Mongolian gerbils (Meriones unguiculatus), a 5-day treatment with a daily intramuscular dose of 100 mg kg−1 aminoxanide resulted in a 72.5% oocyst excretion inhibition, statistically equivalent to 75.5% in gerbils treated with a 4-fold lower oral dose of NTZ. Cryptosporidium parvum-induced intestinal pathology and inflammation were improved. Aminoxanide provides an injectable form of TIZ that NTZ was unable to do and is a promising drug for which optimization of the formulation should be further explored. These results represent a first promising step towards the goal of developing a parenteral treatment for cryptosporidiosis.
隐孢子虫病是一种以大量腹泻为特征的胃肠道疾病。虽然没有其他经美国食品和药物管理局 (FDA) 批准的治疗隐孢子虫病的替代方法，但硝唑尼特 (NTZ) 可被认为具有部分疗效。在免疫抑制的情况下，可能会发生严重和/或播散性隐孢子虫病，患者应接受肠外治疗。为了实现开发隐孢子虫病肠外治疗的目标，本研究旨在研究氨基氧硝唑在体外和体内抗隐孢子虫的活性。这种新的 L-叔亮基噻唑啉是替硝唑 (TIZ) 的可溶性前药，TIZ 是 NTZ 的主要代谢物。氨基氧硝唑在感染隐孢子虫的 HCT-8 细胞中的 50%抑制浓度为 1.55 μm（±0.21），证实了其对感染隐孢子虫的免疫抑制蒙古沙鼠的良好疗效。在感染隐孢子虫的免疫抑制蒙古沙鼠中，5 天每天肌内注射 100mg/kg 氨基氧硝唑治疗，可抑制卵囊排泄 72.5%，与口服 4 倍低剂量 NTZ 治疗的沙鼠等效。隐孢子虫引起的肠道病理和炎症得到改善。氨基氧硝唑提供了一种注射用替硝唑，NTZ 无法做到这一点，是一种有前途的药物，应进一步探索其制剂的优化。这些结果代表了开发隐孢子虫病肠外治疗的一个有希望的第一步。
