Geraniol as a promising natural compound in the treatment of cryptosporidiosis: In vivo efficacy and safety in immunosuppressed mice

Abstract

Cryptosporidiosis remains a significant health concern, particularly in immunocompromised hosts, for whom available treatments may have limited efficacy. This study evaluated the therapeutic effects of geraniol (GR), alone and in combination with nitazoxanide (NZ), in immunosuppressed mice experimentally infected with Cryptosporidium parvum. The mice were treated in groups with varying doses of GR (25 and 50 mg/kg), NZ (100 mg/kg), and their combination for 7 days. Treatment effects were assessed based on fecal oocyst shedding, intestinal antioxidant enzyme activities, Th1-associated cytokine gene expression, and selected hepatic and renal biochemical markers. GR significantly reduced oocyst shedding and improved antioxidant and immune-related parameters compared with untreated infected/immunosuppressed mice (p < 0.01). The combination of GR with NZ produced a greater reduction in oocyst shedding than either treatment alone, with the GR 50 mg/kg + NZ 100 mg/kg regimen producing the greatest overall effect (p < 0.001). The combined treatment was also associated with restoration of CAT and SOD activities and increased expression of IL-12 and IFN-γ (p < 0.001). No evident treatment-related hepatic or renal toxicity was observed based on the evaluated biochemical markers. Overall, these findings provide preliminary experimental evidence that GR, particularly in combination with NZ, may warrant further investigation as an adjunctive approach for cryptosporidiosis. However, validation in additional animal models and ultimately well-designed clinical studies is required.