Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

The effect of Nigella sativa oil- and wheat germ oil-loaded metal organic frameworks on chronic murine toxoplasmosis.

Treatment of chronic toxoplasmosis is challenging as the available drugs are effective only in the acute stage. Therefore, the current study aimed to investigate Nigella sativa oil (NSO) and wheat germ oil (WGO) loaded on copper-benzene tricarboxylic acid metal organic framework (Cu-BTC MOF) for treating chronic toxoplasmosis in a murine model. Eighty mice were divided into 8 groups (G); uninfected untreated negative control (GI), infected untreated positive control (GII), infected and treated with: Spiramycin (GIII), Spiramycin@Cu-BTC (GIV), Cu-BTC (GV), WGO@Cu-BTC (GVI), NSO@Cu-BTC (GVII) and combined WGO+NSO@Cu-BTC (GVIII). The infected groups were orally inoculated with 10 Toxoplasma gondii Me49 strain cysts/mouse. All drugs were orally administered for 14 consecutive days starting 8 weeks post-infection (wpi). The therapeutic efficacy was evaluated by parasitological (survival rate of mice and brain cyst burden) and histopathological (brain, liver, kidney, eye) parameters. At the end of 2-weeks therapy, the highest therapeutic outcome was achieved with GVII and GVIII exhibiting 100% survival, 64.3% and 51.4% reduction of brain cysts, and an apparent amendment of pathological insults. In the next place was GVI with 90% survival, 49.5% reduction of cysts and marked amelioration of pathological lesions. Meanwhile, GIII and GIV showed 80% survival, 42.4% and 41.8% reduction of cysts as well as minimal to moderate alleviation of tissue damage. The lowest effect was obtained with GV resulting in 70% survival and 24.4% reduction of cysts. The current results support the assertion that the new metal-based nanocomposites can be promising remedies of chronic toxoplasmosis particularly if conjugated with natural herbal extracts as NSO and WGO.

Study on the effect of an ion channel inhibitor "Fluralaner" on Echinococcus granulosus protoscolices and metacestode layers in vitro.

Hydatid disease has a great impact on public health, causing high morbidity and mortality. Main lines of treatment include surgery, which mostly requires the installation of a scolicidal agent into hydatid cysts to prevent dissemination. Alternatively, medical treatment involves the use of benzimidazole drugs; however, the results are not satisfactory, and new drug compounds are urgently needed. Fluralaner is a potent inhibitor of GABA-gated chloride channels and L-glutamate-gated chloride channels (GluCls) providing immediate and persistent flea, tick and mite control in dogs after a single oral dose. Researches previously identified different genes encoding ion channels in Echinococcus granulosus, making ion channel inhibitors a promising target for treating hydatid disease. Thus, the present study aimed to evaluate the effect of fluralaner on protoscolices and metacestode layers. Parasite materials (Protoscolices, Metacestodes layers) were exposed to different concentrations of the drug ranging from "12.5-100 ug/ml" and examined for viability after 1, 6 and 24 h. Morphological and ultrastructural alterations were recorded by both light and electron microscopies. Immunohistochemical staining confirmed caspase-3 activation as an indicator of apoptosis- induced therapy. The treated protoscolices and metacestode layers showed loss of the viability, the formation of vacuoles and lipid droplets, separation of the germinal layer, and damage in the laminated layer; apoptosis was prominent after treatment. These findings revealed that fluralaner has a potent scolicidal activity and suggested its therapeutic potential against hydatid disease. Further evaluations for animals and human use in the treatment and prevention of hydatid disease are needed.