Anti-Cryptosporidium efficacy of Citrus sinensis peel extract: Histopathological and ultrastructural experimental study

Cryptosporidium spp. is ubiquitous zoonotic protozoan parasite that infects wide series of vertebrate hosts. Absence of host-specificity, excretion of large numbers of directly infective oocysts and their resistance to various chemicals are some factors that pave the way for ubiquity of Cryptosporidium in nature (Feng et al., 2018; Jain et al., 2019).

Although being recognized as self-limited disease in immunocompetent individuals, cryptosporidiosis is a major cause of persistent life-threatening diarrhea in children and immunocompromised patients with subsequent significant morbidity and mortality (Ghomashlooyan et al., 2015). Furthermore, Cryptosporidium spp. occur significantly more often in patients with colorectal cancer suggesting possible association (Sulżyc-Bielicka et al., 2018; Zhang et al., 2020).

The parasite represents major public health challenge taking into consideration the limitations in management options. Several drugs either singly, or in combinations had been evaluated for treatment including paromomycin, fluoroquinolone, azithromycin, as well as spiramycin with variable efficiency (Sparks et al., 2015; Diptyanusaa and Saric, 2021). Nitazoxanide, the only FDA-approved drug for treating cryptosporidiosis, shows limited efficacy in treating severely immunocompromised such as AIDS patients, and malnourished infants (Checkley et al., 2015). This raised the need for searching reasonable alternatives.

Recently, there has been growing interest in developing new antiparasitics from medicinal plants, including Citrus sinensis (C. sinensis), popularly known as sweet orange. Leaves and peels of C. sinensis are rich in variable metabolites of major pharmacological, and industrial significance such as essential oils, hesperidin (HSP), coumarins, furanocoumarins, and polymethoxy flavones (Ho et al., 2010; Bahaa.El.Deen and Sadek, 2014).

Some of these metabolites possess major analgesic anti-inflammatory, antibacterial, antiviral, antifungal, antioxidant, anticarcinogenic, as well as hypocholesterolemic properties (Favela-Hernández et al., 2016).

Moreover, Citrus plant showed promising antiparasitic efficiency. For example, it displayed potential antimalarial (Bhat and Surolia, 2001), antitrypanosomal (Habila et al., 2010), and antischistosomal effect (Allam and Abuelsaad, 2013). Its essential oils also proved insecticidal activity against some mosquitoes and flies (Murugan et al., 2012; Kumar et al., 2012).

To our knowledge, no data have been mentioned on the efficiency of Citrus sinensis peel extract on Cryptosporidium spp. This attracted our interest to conduct the study to evaluate the in vivo anti-Cryptosporidium efficiency of Citrus sinensis peel extract concerning parasitological, pathological and ultrastructural parameters in murine model of infection.

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