Schistosomiasis mansoni: A new therapeutic target for ubiquinol, a natural inhibitor of neutral magnesium-dependent sphingomyelinase in murine model.

Abstract

Constituting the host-parasite interface and playing a censorious role in host immune response modulation and parasite survival, tegument represents a crucial target for many antischistosomal drugs. Sphingomyelin forms a stable outer leaflet of tegumental membrane-lipid bilayer. Neutral magnesium‏-dependent sphingomyelinase (Mg2+-nSMase) is a key enzyme in sphingomyelin breakdown was identified in schistosomes. We investigated the in vivo efficacy of ubiquinol, a natural inhibitor of Mg2+-nSMase, in free and niosomes-encapsulated forms, through five-day and 15-day regimens on the early and late Schistosoma mansoni parasitic stages, respectively, compared to PZQ. Oral administration of 300 mg/kg/day ubiquinol-encapsulated niosomes (U-N) showed significant deterioration of the parasitic growth and development in the term of reduction of lung schistosomula burden (39.12%), adult worm burden (50.81%), hepatic and intestinal tissue-egg counts (80.89% and 75.54%, respectively). PZQ and free ubiquinol regimens reported reductions in lung schistosomula counts (45.36% and 22.90%, respectively) and total worm burdens of 86.28% and 24.58%, respectively. U-N therapy revealed worms de-pairing and remarkable diminution in female worms’ perimeters and fecundity. Scanning electron microscope revealed disruption of tegumental ridges with excessive longitudinal corrugation. Transmission electron microscope showed testicular and ovarian parenchymal degeneration, signs of immaturity and cell apoptosis. Indirect immunofluorescence assay approved parasite's tegumental changes. Remarkable reduction of granulomas size with amelioration of hepatic pathology and fibrosis were assumed to be attributed to the anti-inflammatory and anti-oxidant properties of ubiquinol. These findings with the drug safety profile suggest that U-N could be a promising candidate for a new antischistosomal drug development.