Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

Abstract

Cryptosporidiosis is one of the most frequent food and water-borne diseases. The disease might be life-threatening in immunosuppressed patients. Unfortunately, the only approved drug, nitazoxanide, is with variable efficacies, particularly in malnourished children and immunocompromised patients. Therefore, there is a need to discover an alternative treatment that could be achieved by targeting the metabolic pathways. One of the important enzymes in the glycolysis pathway of C. parvum is triosephosphate isomerase, which could be hindered by the proton pump inhibitor (PPI) omeprazole. In this study, omeprazole was repurposed against C. parvum infection in experimentally immunosuppressed mice. This study was conducted on five mice groups (n = 10). Group I (Normal Control), group II (Infected Control): Mice were infected orally with 1×105 C. parvum oocysts on the 15th day of DEX induced immunosuppression. Group III (NTZ-treated): infected and treated by NTZ. Group IV (Omeprazole-treated), and lastly, Group V (NTZ + Omeprazole-treated). The result obtained with omeprazole alone was better than nitazoxanide regarding oocyst shedding reduction percentages (84.9% & 56.1%, respectively). Also, it was better regarding restoration of histopathological and ultrastructural architectures, improvement of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and renal functions (urea and creatinine), and the reduction of C. parvum triosephosphate isomerase (TIM) gene expression by RT-PCR. However, the best results were obtained with the combined treatment. Hence, omeprazole could be considered a novel drug option to treat this life-threatening parasitic infection either alone or combined with NTZ, especially in immunosuppressed patients.