Repurposing the proton pump inhibitor "Rabeprazole sodium" in the treatment of acute experimental murine...

Toxoplasmosis is a major health concern with serious consequences in immunocompromised patients and pregnant women. The currently available anti-Toxoplasma therapies have significant limitations including toxicity and emerging resistance. Therefore, there is an urgent need for safe and effective alternative drugs. Repurposing of proton pump inhibitors (PPI) represents a promising strategy because of their reported antiparasitic activities. This study aimed to evaluate the potential therapeutic effect of rabeprazole sodium, a PPI, in a murine model of acute toxoplasmosis in comparison with trimethoprim-sulfamethoxazole (TMP-SMZ). The employed mice were allocated into five groups. Uninfected control, Infected untreated, Infected DMSO-treated, Infected TMP-SMZ-treated, and Infected rabeprazole-treated. Two regimens of rabeprazole were applied; seven-day and ten-day regimens. The efficacy of drugs was assessed through various parameters: parasite load in peritoneal fluid and tissue impression smears, tachyzoite viability rate, scanning and transmission electron microscopy, histopathological and immunohistochemical studies and assay of cytoplasmic and apicoplast triose phosphate isomerase (TPI) enzyme activity. The ten-day regimen of rabeprazole elicited a statistically significant decrease in parasite count in peritoneal fluid, liver and spleen impressions with reductions of 92.16%, 93.83% and 90.91%, respectively. Additionally, tachyzoite viability and TPI activity were significantly affected, and numerous ultrastructural deformities were captured. Favorably, it has obviously ameliorated the tissue pathology through anti-apoptotic impacts and anti-inflammatory properties. To our knowledge, this is the first in vivo study to repurpose rabeprazole against acute toxoplasmosis. In this context, rabeprazole demonstrated superior efficacy to TMP-SMZ enforcing its potential as a promising safe, alternative therapeutic regimen for toxoplasmosis.