Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection

Abstract

Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma. Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against S. mansoni ex vivo and in mice harboring either chronic or early S. mansoni infection. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In a mouse infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10-100 mg/kg) or by oral gavage (100-400 mg/kg), and we studied the influence of drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, EC50 and EC90 values revealed that diminazene is able to kill both immature and adult parasites, and its effect was time- and concentration-dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the tegument of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and it improves liver injury caused by Schistosoma eggs.

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

“…In both stages of infections, amiodarone was administered using a single oral dose (400 mg/kg) or once daily for five consecutive days (100 mg/kg/day). It should be noted that these doses were selected because they are often used in studies on approaches to drug discovery for schistosomiasis [ 10 , 11 , 12 , 13 , 14 , 15 ]. For comparison, data obtained with the drug of reference (praziquantel at 400 mg/kg) in animals with either chronic or early infections are also presented.…”

“…Thus, our present data are consistent with and expand upon those from these findings and encourage further exploration of cardiovascular agents to search for new antischistosomal agents. In terms of the methodologies employed, the in vitro phenotypic screening, route of administration (oral), dosing regimen applied (400 mg/kg or 100 mg/kg/day), and model of S. mansoni infection (early and chronic) are in accordance with various studies for antischistosomal drug discovery [ 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…For comparison, praziquantel was administered at 400 mg/kg to groups of five S. mansoni -infected animals in the same period. As a note, the doses used of amiodarone and praziquantel were based on the protocols recommended for experimental schistosomiasis [ 10 , 11 , 12 , 13 , 14 ]. For each treatment period, infected but only vehicle-treated mice (five mice per group) served as controls.…”

“…In this context, finding new indications for existing drugs, also known as drug repositioning or reprofiling, may be considered a promising strategy to accelerate drug discovery and development in combating schistosomiasis [ 8 , 9 ]. In recent years, using an in vitro phenotypic screening assay against S. mansoni adult worms, we have screened many clinical drugs that have been approved by either the US Food and Drug Administration or its foreign equivalents, and identified several promising compounds [ 10 , 11 , 12 , 13 , 14 , 15 ]. Among these, from a screening of 13 diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects in vitro and in vivo in a mouse model of schistosomiasis [ 15 ].…”

Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent

“…Activity against schistosomula was determined as described previously [38,39] . Briefly, S. mansoni cercariae were harvested from infected snails and mechanically transformed to schistosomula using a vortex mixer.…”