Effect of Simultaneous and/or Consecutive Administration of the Broad Spectrum Anthelmintic Flubendazole together with Praziquantel in Experimental Schistosoma mansoni Infection

William, Samia; Guirguis, Fatem; Nessim, Nevine Guirguis

doi:10.1055/s-0031-1297145

Cited by 6 publications

(8 citation statements)

References 15 publications

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“…The anthelmintic drug FBZ has broad spectrum action against tapeworm infections. In vivo studies (in mice) demonstrated its activity in reducing numbers of adult parasites of S. mansoni [44,45]. Here, FBZ was more potent than PZQ or AS against NTS.…”

Section: Discussionmentioning

confidence: 99%

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

et al. 2019

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Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.

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Section: Discussionmentioning

confidence: 99%

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

et al. 2019

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“…four fold the therapeutic dose in mice (125 mg/kg) based on Food and Drug Administration guidelines by converting the human dose to those for experimental animals. PZQ was given in a dose of 500 mg/kg for 2 days according to William et al (2003).…”

Section: Drug Administrationmentioning

confidence: 99%

Evaluation of the bioassay of Commiphora molmol extract (Mirazid) against praziquantel in experimentally infected mice with Schistosoma mansoni

Aziz

Aziz²

2017

Journal of Veterinary Medical Research

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Schistosoma mansoni worms inhabit the portal triad affecting blood elements. Therefore, the current study aimed to compare ameliorative effects of Commiphora molmol extract (Mirazid, MZD) and praziquantel (PZQ) on some biochemical parameters in S. mansoni-infected mice. Accordingly, Swiss albino mice (n=72) were used and were divided into 4 equal groups; 18 mice each. Group (1) was uninfected non-treated control. Mice in infected groups administered 100 S. mansoni cercariae/mouse. Group (2) contained infected non-treated mice. Group (3) was infected and treated with MZD at a dose of 500 mg/kg for 5 successive days. Group (4) was infected and treated with PZQ in a dose of 500 mg/kg for 2 successive days. Treatment started 7 weeks post infection (WPT) by the oral route. Blood samples were collected at the 1st, 2nd and 4th weeks post treatment for liver functions (ALT, AST and ALP), kidney functions tests (blood urea and serum creatinine) and cholinergic function (serum cholinesterase level). PZQ ameliorated activities of serum enzymes; alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase more than MZD compared to infected untreated group. PZQ significantly decreased ALT at 1, 2 and 4 WPT as well as AST and ALP activity at 2 and 4 WPT whereas, MZD resulted in significant reduction in ALT activity at the 1st, 2nd and 4th WPT. AST and ALP activities appeared at the 2nd and 4th WPT. PZQ caused progressive significant reduction in elevated levels of urea and creatinine at the 1st, 2nd and 4th WPT, respectively that produced by MZD. PZQ and MZD induced a significant elevation in the level of AChE. Such effect was early detected MZD, and it was showed at the 2nd and 4th WPT for PZQ. It was concluded that PZQ and MZD were safe drugs with no adverse biochemical effects on S. mansoni-infected treated mice with potential action done by PZQ rather than MZD.

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“…On the other hand, albendazole and mebendazole, the main anti-echinococcal drugs, have no impact on S. mansoni (Schmidt, 1998). In contrast, flubendazole, a mebendazole-derivative, was active against S. mansoni in experimentally infected mice (Nessim et al 2000; Williams et al 2003), and another benzimdazole, triclabendazole, was active against Fasciola hepatica (Robinson et al 2001). As for Echinococcus , F. hepatica was susceptible to nitazoxanide treatment in vitro , and clinical studies showed that nitazoxanide could be used for the treatment of fasciolasis in children and adults (reviewed in Hemphill et al 2006).…”

Section: Relevance Of Echinococcus Metacestode Screening Models For Omentioning

confidence: 99%

Echinococcusmetacestodes as laboratory models for the screening of drugs against cestodes and trematodes

Hemphill¹,

Lundström‐Stadelmann²,

Scholl³

et al. 2009

Parasitology

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Among the cestodes, Echinococcus granulosus, Echinococcus multilocularis and Taenia solium represent the most dangerous parasites. Their larval stages cause the diseases cystic echinococcosis (CE), alveolar echincoccosis (AE) and cysticercosis, respectively, which exhibit considerable medical and veterinary health concerns with a profound economic impact. Others caused by other cestodes, such as species of the genera Mesocestoides and Hymenolepis, are relatively rare in humans. In this review, we will focus on E. granulosus and E. multilocularis metacestode laboratory models and will review the use of these models in the search for novel drugs that could be employed for chemotherapeutic treatment of echinococcosis. Clearly, improved therapeutic drugs are needed for the treatment of AE and CE, and this can only be achieved through the development of medium-to-high throughput screening approaches. The most recent achievements in the in vitro culture and genetic manipulation of E. multilocularis cells and metacestodes, and the accessability of the E. multilocularis genome and EST sequence information, have rendered the E. multilocularis model uniquely suited for studies on drug-efficacy and drug target identification. This could lead to the development of novel compounds for the use in chemotherapy against echinococcosis, and possibly against diseases caused by other cestodes, and potentially also trematodes.

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Effect of Simultaneous and/or Consecutive Administration of the Broad Spectrum Anthelmintic Flubendazole together with Praziquantel in Experimental Schistosoma mansoni Infection

Cited by 6 publications

References 15 publications

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

Evaluation of the bioassay of Commiphora molmol extract (Mirazid) against praziquantel in experimentally infected mice with Schistosoma mansoni

Echinococcusmetacestodes as laboratory models for the screening of drugs against cestodes and trematodes

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