Curative and Protective Effects of Fenugreek Seeds Extract-Loaded Zinc Oxide Nanoparticles Against Lung Damage and Intestinal Dysplasia Induced by Experimental Cryptosporidiosis.

Cryptosporidiosis is a global health concern that causes mortality and morbidity in children and immunocompromised patients. The currently available anticryptosporidial agent, nitazoxanide (NTZ), has limited efficacy in cases of low immunity. This study aimed to evaluate the curative and protective effects of fenugreek (FNK) extract- loaded zinc oxide nanoparticles (ZnO NPs) against lung damage and intestinal dysplasia induced by experimental cryptosporidiosis. Eighty mice were divided into eight groups (ten mice per subgroup): non-infected non-treated, infected non-treated, infected receiving ZnO NPs, infected receiving NTZ, infected receiving FNK extract, infected receiving FNK- loaded ZnO NPs, infected receiving NTZ- loaded ZnO NPs, and infected receiving both NTZ and FNK extract- loaded ZnO NPs. Assessment parameters included oocyst shedding counts, histopathological and cyclin D1 immunohistochemical analysis in intestinal and lung tissues, evaluation levels of serum IL-17 levels and tissue oxidative stress markers (MDA, NO, SOD, and CAT), and expression of apoptotic gene markers (BCL-2 and caspase-3). The results demonstrated that treatment with ZnO NPs loaded NTZ and FNK extract yielded the most significant reduction in oocyst shedding, along with marked improvement in lung damage and intestinal dysplasia. Furthermore, this treatment was associated with negative cyclin D1 expression, near-normal levels of IL-17 and oxidative stress markers, and normalized BCL-2 and caspase-3 expression. Thus, the curative and protective activity of NTZ in cryptosporidiosis was enhanced when combined with FNK extract and loaded onto ZnO NPs.