ABSTRACT
Cryptosporidium is a widely distributed food and water-borne enteric protozoan that affects a wide range of vertebrates, resulting in life-threatening consequences, particularly in immunocompromised hosts. The lack of effective anti-cryptosporidial drugs may be related to the parasite's unique intestinal location, plus the lack of studies on the process by which the protozoan is able to impair intestinal cellular function. The present work aimed to assess the effect of clofazimine (CFZ), an FDA-approved drug for the treatment of leprosy, as an anti-cryptosporidial drug, using transmission electron microscopy (TEM) and an immunocompromised mouse model. The affected intestinal mucosa with parasitic stages in the infected non-treated group showed signs of severe cellular degeneration, including the loss of tight junctions, deformed and damaged microvilli and irregularly distributed nuclei with a severely vacuolated cytoplasm. Comparatively, nitazoxanide (NTZ) monotherapy showed the lowest efficacy as the drug was associated with the lowest rate of oocyst shedding. In addition, NTZ treatment failed to achieve the return of complete cellular function; abnormalities were evident in the microvilli, cytoplasmic organelles and nuclear features. Clofazimine demonstrated an improvement of the mucosal cellular components, including mitochondria and significantly reduced oocyst shedding. Combined treatment with low-dose CFZ and half-dose NTZ resulted in a significant improvement in the enterocyte cellular structures with an absence of intracellular parasitic stages. These results indicate that CFZ, a safe and readily prescribed drug, effectively reduces cryptosporidiosis when used in combination with only half the dose of NTZ. Used in combination, these drugs were shown to be efficient in regaining intestinal cellular activity following Cryptosporidium-induced functional damage in an immunocompromised mouse model.
ABSTRACT
Eighty adult male hamsters were used in this study, 20 of them were divided equally into a noninfected, nontreated control group and chronic lead exposed groups, which were given lead acetate intraperitoneally, dissolved in distilled water, 2 mg/kg/day for seven weeks. Then, two experiments were carried out on the remaining animals. Each experiment included 30 animals and was divided equally into three groups. Experiment A was carried out on the following groups: Schistosoma mansoni infected group, S. mansoni infected and chronic lead exposed group and S. mansoni infected, chronic lead exposed and 'Antox' treated group. Experiment B was done following the same design except that infection was carried out using Schistosoma haematobium cercaria. Chronic lead exposure of Schistosoma infected groups showed significant reductions in worm burden, tissue egg load and ova excretion in stool, liver and intestine. Compared with the control group, there were insignificant increases in serum and hepatic glutathione and malondialdehyde levels and a significant increase in hepatic 8-oxodeoxyguanosine phosphate (8-Ox-Dg) levels in Schistosoma infected groups. However, there was a significant increase in hepatic and blood lead levels, oxidative stress parameters and in the hepatic 8-Ox-Dg level in Schistosoma infected and chronic lead exposed groups as compared with their corresponding Schistosoma only infected groups. This study revealed a significant reduction in oxidative stress parameters as well as in blood and hepatic lead levels and in hepatic 8-Ox-Dg levels after giving Antox to the Schistosoma infected and chronic lead exposed groups. However, Antox increased insignificantly all the parasitological parameters studied in the Schistosoma infected and chronic lead exposed groups.
