In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of  Schistosoma mansoni

Context: (−)-6,6′-Dinitrohinokinin (DNHK) display remarkable antiparasitic activity and was, therefore, incorporated into a nanoparticle formulation.Objective: Incorporation of DNHK in poly lactic-co-glycolic acid (PLGA) nanoparticles aiming to improve its biological activities.Materials and methods: Synthesis, characterization and incorporation of DNHK into glycolic acid (PLGA) nanoparticles by nanoprecipitation method. The nanoparticles were characterized by ultraviolet-visible spectroscopy, X-ray diffraction, field emission electron microscopic scanning mansoni (FESEM), and dynamic light scattering (DLS). For the in vitro test with Schistosoma mansoni, the DNHK-loaded PLGA was diluted into the medium, and added at concentrations 10–200 µM to the culture medium containing one adult worm pair. The parasites were kept for 120 h and monitored every 24 h to evaluate their general condition, including: pairing, alterations in motor activity and mortality.Results: The loaded PLGA nanoparticles gave an encapsulation efficiency of 42.2% and showed spherical characteristics in monodisperse polymeric matrix. The adult worm pairs were separated after 120 h of incubation for concentrations higher than 50 µM of DNHK-loaded PLGA. The groups incubated with 150 and 200 µM of DNHK-loaded PLGA for 24 and 120 h killed 100% of adult worms, afforded LC50 values of 137.0 ± 2.12 µM and 79.01 ± 1.90 µM, respectively, which was similar to the effect displayed by 10 µM of praziquantel.Discussion and conclusions: The incorporation of DNHK-loaded showed schistosomicidal activity and allowed its sustained release. The loaded PLGA system can be administered intravenously, as well as it may be internalized by endocytosis by the target organisms.

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“…Pereira et al. ( 2015 ) reported the effect of DNHK-free on adult worms of S. mansoni , and the LC 50 value was 103.9 ± 3.6 µM at 24 h.…”

Section: Resultsmentioning

confidence: 99%

“…( 2009 ) by partial synthesis of (−)-hinokinin, displayed schistosomicidal activity against S. mansoni in both in vitro and in vivo (Pereira et al. 2015 ). Therefore, based on the schistosomicidal effect of DNHK, this work incorporates DNHK in PLGA nanoparticles in an attempt to improve the schistosomicidal activity of this compound.…”

Section: Introductionmentioning

confidence: 99%

In vitro schistosomicidal activity of the lignan (−)-6,6′-dinitrohinokinin (DNHK) loaded into poly(lactic-co-glycolic acid) nanoparticles against Schistosoma mansoni

Lima

Lucarini

Luz

et al. 2017

Pharmaceutical Biology

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“…Due to unavailability of a schistosomiasis vaccine, the common strategy for treatment and control is mainly based on chemotherapy (Pereira et al 2015). Praziquantel (PZQ) is the drug of choice for large-scale treatment of schistosomiasis as it is a safe and cheap therapy (Cheng et al.…”

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confidence: 99%

Ultrastructural alterations in Schistosoma mansoni juvenile and adult male worms after in vitro incubation with primaquine

Kamel

Bayaumy

2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND Praziquantel has been cited as the only drug for treating schistosomiasis. However, concerns over drug resistance have encouraged the search for novel drug leads. The antimalarial drug primaquine possesses interesting anti-schistosmal properties.OBJECTIVES This study is the first to document the potential role of primaquine as a schistosomicide and the ultrastructural changes induced by primaquine on juvenile or adult male worms of Schistosoma mansoni.METHODS Ultrastructural alterations in the tegumental surface of 21-day-old juvenile and adult male worms of S. mansoni were demonstrated following primaquine treatment at different concentrations (2, 5, 10, 15, and 20 µg/mL) and incubation periods (1, 3, 6, 24, and 48 h) in vitro, using both scanning and transmission electron microscopy.FINDINGS At low concentrations (2, 5, and 10 µg/mL) both juvenile and adult male worms were alive after 24 h of incubation, whereas contraction, paralysis, and death of all worms were observed after 24 h of drug exposure at 20 µg/mL. The tegument of juvenile and adult male worms treated with primaquine exhibited erosion, peeling, and sloughing. Furthermore, extensive damage of both tegumental and subtegumental layers included embedded spines, and shrinkage of muscles with vacuoles. The in vitro results confirmed that primaquine has dose-dependent effects with 20 µg/mL as the most effective concentration in a short incubation period.MAIN CONCLUSIONS The schistosomicidal activity of primaquine indicates that this drug possesses moderate in vitro activity against juvenile and adult male worms, since it caused high mortality and tegumental alterations. This study confirmed that the antimalarial drug primaquine possesses anti-schistosomal activity. Further investigation is needed to elucidate its mechanism of action.

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“…Similarly, another study showed that (-)-6,6'-dinitrohinokinin (DNK) at 200μM killed 100% of adult worms within 24h and had LC 50 values of 103.9±3.6 and 102.5±4.8μM at 24 and 72h, respectively (33) . Incubation of adult S. mansoni worms with CO-ArNp at 20-40μg/ml for 48-72h also killed all worms (31) .…”

Section: Discussionmentioning

confidence: 99%

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes

Hassan

Abdel-Rahman

Ibrahim

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Introduction:We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. Methods: Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC 50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC 50 doses of venom. Results: The LC 50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50% , respectively. LC 50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. Conclusions: The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

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In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

Cited by 30 publications

References 42 publications

In vitro schistosomicidal activity of the lignan (−)-6,6′-dinitrohinokinin (DNHK) loaded into poly(lactic-co-glycolic acid) nanoparticles against Schistosoma mansoni

In vitro schistosomicidal activity of the lignan (−)-6,6′-dinitrohinokinin (DNHK) loaded into poly(lactic-co-glycolic acid) nanoparticles against Schistosoma mansoni

Ultrastructural alterations in Schistosoma mansoni juvenile and adult male worms after in vitro incubation with primaquine

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes

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