scholarly journals Ginger (Zingiber Officinale)-derived nanoparticles in Schistosoma mansoni infected mice: Hepatoprotective and enhancer of etiological treatment

2021 ◽  
Vol 15 (5) ◽  
pp. e0009423
Author(s):  
Wegdan M. Abd El Wahab ◽  
Ayman A. El-Badry ◽  
Soheir S. Mohmoud ◽  
Yaser A. El-Badry ◽  
Mohamed A. El-Badry ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Therapeutic Effect ◽  
Worm Burden ◽  
Zingiber Officinale ◽  
Egg Load ◽  
Therapeutic Drug ◽  
Slight Reduction ◽  
Prophylactic Drug ◽  
Egg Density ◽  
Therapeutic Doses

Background Nanotechnology has been manufactured from medicinal plants to develop safe, and effective antischistosmal alternatives to replace today’s therapies. The aim of the study is to evaluate the prophylactic effect of ginger-derived nanoparticles (GNPs), and the therapeutic effect of ginger aqueous extract, and GNPs on Schistosoma mansoni (S. mansoni) infected mice compared to praziquantel (PZQ), and mefloquine (MFQ). Methodology/principal findings Eighty four mice, divided into nine different groups, were sacrificed at 6th, 8th, and 10th week post-infection (PI), with assessment of parasitological, histopathological, and oxidative stress parameters, and scanning the worms by electron microscope. As a prophylactic drug, GNPs showed slight reduction in worm burden, egg density, and granuloma size and number. As a therapeutic drug, GNPs significantly reduced worm burden (59.9%), tissue egg load (64.9%), granuloma size, and number at 10th week PI, and altered adult worm tegumental architecture, added to antioxidant effect. Interestingly, combination of GNPs with PZQ or MFQ gave almost similar or sometimes better curative effects as obtained with each drug separately. The highest therapeutic effect was obtained when ½ dose GNPs combined with ½ dose MFQ which achieved 100% reduction in both the total worm burden, and ova tissue density as early as the 6th week PI, with absence of detected eggs or tissue granuloma, and preservation of liver architecture. Conclusions/significance GNPs have a schistosomicidal, antioxidant, and hepatoprotective role. GNPs have a strong synergistic effect when combined with etiological treatments (PZQ or MFQ), and significantly reduced therapeutic doses by 50%, which may mitigate side effects and resistance to etiological drugs, a hypothesis requiring further research. We recommend extending this study to humans.

scholarly journals Effects of Callistemon citrinus aqueous extract on prepatent and patent infections with Schistosoma mansoni in experimentally infected mice

2018 ◽  
Vol 93 (04) ◽  
pp. 424-433
Author(s):  
S.A. El-Refai ◽  
A.F. Atia ◽  
S.F. Mahmoud
Keyword(s):  
Schistosoma Mansoni ◽  
Aqueous Extract ◽  
Worm Burden ◽  
Total Bilirubin ◽  
Liver Enzymes ◽  
Control Strategies ◽  
Chemotherapeutic Agents ◽  
Egg Load ◽  
Hepatic Granuloma

AbstractSchistosomiasis is a chronic debilitating parasitic disease that causes hepatic damage and is known to be endemic in developing countries. Recent control strategies for schistosomiasis depend exclusively on chemotherapeutic agents, specifically praziquantel. Unfortunately, praziquantel has low efficacy in the early phase of infection, and resistance to treatment is increasingly reported. The aim of this work was to find an alternative treatment by assessing the in vivo activity of aqueous extract of Callistemon citrinus against Schistosoma mansoni in both prepatent and patent phases in experimentally infected mice. The study was conducted on 80 male BALB/c albino mice divided into eight groups. Callistemon was administered at a dose of 200 mg/kg on days 14 and 45 post infection as a single therapy and in combination with praziquantel. Porto-mesenteric worm burden, hepatic and intestinal egg counts, hepatic granuloma number and diameter, and oogram pattern were assessed to evaluate the anti-schistosomal properties of C. citrinus. Liver enzymes and total bilirubin were tested to assess hepatoprotective effects. Results revealed that the use of C. citrinus was associated with a significant decrease in worm burden and tissue egg load together with an increased percentage of dead eggs. In addition, there was a significant reduction in granuloma formation. Callistemon also led to a significant improvement in liver function. The best results were obtained when C. citrinus was given in the prepatent phase of infection and when combined with praziquantel. Although the effects of C. citrinus are considered to be promising, further studies using different extracts, active ingredients and doses are needed.

Immunization efficacy of ozone-exposed cercariae against subsequent Schistosoma mansoni challenge infection

2011 ◽  
Vol 61 (3) ◽  
pp. 289-301
Author(s):  
Azza H. Mohamed
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Structural Changes ◽  
Relative Weight ◽  
Challenge Infection ◽  
Total Leukocyte Count ◽  
Post Challenge ◽  
Igg Antibody ◽  
Sem Images ◽  
Infected Control

AbstractCD1 mice were immunized subcutaneously with 20 ozone-exposed (70μg/ml, 1 minute exposure) Schistosoma mansoni cercariae weekly/three weeks. The efficacy of immunization was assessed 10 weeks post challenge infection by the determination of the worm burden, ova count, oogram, granuloma diameter, IgG reactions against soluble egg antigen (SEA) and tegument structural changes of recovered worms that are immunized. A reduced worm length and a reduction in worm burden were observed in the immunized group as compared to the infected not immunized group. Moreover, no ova were found in liver and intestine from the immunized mice as compared with infected control mice. Also, immunization with ozonated cercariae showed a decrement in the mean relative weight of liver and spleen. Total leukocyte count was increased in the immunized animal as compared to the infected control. The level of total IgG antibody against SEA decreased in immunized mice as compared with the infected control mice. Scanning electron microscope (SEM) images of worms recovered 10 weeks post challenge from the immunized group revealed extensive tegumental destruction. This study underlines the significant role of ozone attenuated cercariae vaccine against S. mansoni infection, which generated specific immunity with a significant level of protection.

scholarly journals Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

2015 ◽  
Vol 59 (6) ◽  
pp. 3501-3508 ◽  
Author(s):  
Gina S. El-Feky ◽  
Wael S. Mohamed ◽  
Hanaa E. Nasr ◽  
Naglaa M. El-Lakkany ◽  
Sayed H. Seif el-Din ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Rate Constant ◽  
Elimination Rate ◽  
New Drugs ◽  
Egg Load ◽  
Potential Cost ◽  
Time Curve ◽  
Content Type ◽  
Mmt Clay

ABSTRACTConsideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and itsin vivoefficacy againstSchistosoma mansoniwere investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.

Mitochondria as a potential target for the development of prophylactic and therapeutic drugs against Schistosoma mansoni infection

2021 ◽  
Author(s):  
Keith Kiplangat Talaam ◽  
Daniel Ken Inaoka ◽  
Takeshi Hatta ◽  
Daigo Tsubokawa ◽  
Naotoshi Tsuji ◽  
...  
Keyword(s):  
Drug Development ◽  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Consumption Rate ◽  
Therapeutic Agent ◽  
Ex Vivo ◽  
Prophylactic Agent ◽  
Therapeutic Drugs ◽  
Pyrvinium Pamoate

Emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni ), makes the development of new antischistosomal drugs urgent. The parasite’s mitochondrion is an attractive target for drug development because this organelle is essential for survival throughout the parasite’s life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercariae motility that have been reported to affect mitochondria-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against motility of schistosomula ( in vitro ) and adults ( ex vivo ). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 Analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% that obtained in the vehicle control. Notably, ascofuranone showed the highest activity with a 98% reduction of the worm burden, suggesting the potential for development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and non-mitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are feasible target for drug development.

scholarly journals Synergistic action of praziquantel and host specific immune response against Schistosoma mansoni at different phases of infection

2004 ◽  
Vol 46 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Fabio Ribeiro ◽  
Rômulo Teixeira de Mello ◽  
Carlos Alberto Pereira Tavares ◽  
John Robert Kusel ◽  
Paulo Marcos Zech Coelho
Keyword(s):  
Immune Response ◽  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Synergistic Action ◽  
Specific Immune Response ◽  
Concomitant Immunity

The interaction between specific immune response to Schistosoma mansoni and praziquantel (PZQ) was studied in mice. In mice harboring concomitant immunity, 6-day-old parasites treated with PZQ were more effectively removed than 24h treated parasites despite both had a significant worm burden reduction when compared with respective treated controls. These results show that PZQ can be effective at the skin and lung stages of parasite's development mainly acting with a established specific immune response, and particularly at the lung phase.

scholarly journals In VivoActivity of Aryl Ozonides against Schistosoma Species

2011 ◽  
Vol 56 (2) ◽  
pp. 1090-1092 ◽  
Author(s):  
Jennifer Keiser ◽  
Katrin Ingram ◽  
Mireille Vargas ◽  
Jacques Chollet ◽  
Xiaofang Wang ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Female Worm ◽  
Lead Compound ◽  
Content Type ◽  
Total Worm Burden

ABSTRACTWe evaluated thein vivoantischistosomal activities of 11 structurally diverse synthetic peroxides. Of all compounds tested, ozonide (1,2,4-trioxolane) OZ418 had the highest activity against adultSchistosoma mansoni, with total and female worm burden reductions of 80 and 90% (P< 0.05), respectively. Furthermore, treatment ofS. haematobium-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound.

scholarly journals Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice

2014 ◽  
Vol 40 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Omaima Mohammed Abou-Shady ◽  
Soheir Sayed Mohammed ◽  
Samar Sayed Attia ◽  
Hebat-Allah Salah Yusuf ◽  
Dina Omar Helmy
Keyword(s):  
Schistosoma Mansoni ◽  
Therapeutic Effect ◽  
Experimental Infection

Schistosoma mansoni Infection in the Rat. I. Worm Burden and Serological Response in Infected, Reexposed, and Antigen-Sensitized Animals

1970 ◽  
Vol 56 (6) ◽  
pp. 1058 ◽  
Author(s):  
Shirley E. Maddison ◽  
Lois Norman ◽  
Sadie J. Geiger ◽  
Irving G. Kagan
Keyword(s):  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Serological Response

scholarly journals Complementary effect of Capparis spinosa L. and silymarin with/without praziquantel on mice experimentally infected with Schistosoma mansoni

2018 ◽  
Vol 55 (1) ◽  
pp. 21-32
Author(s):  
S. S. El-Hawary ◽  
K. F. Taha ◽  
F. N. Kirillos ◽  
A. A. Dahab ◽  
A. A. El-Mahis ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Schistosoma Mansoni ◽  
Hepatic Fibrosis ◽  
Colorimetric Assay ◽  
Quantitative Estimation ◽  
Scar Tissue ◽  
Egg Load ◽  
Total Polyphenols ◽  
Capparis Spinosa ◽  
Serum Aminotransferases

SummarySchistosomiasis remains to be the most common fibrotic disease resulting from inflammation and deposition of scar tissue around trapped parasitic eggs in the liver. Though chemotherapy eradicates matured worms efficiently and prevents the accumulation ofschistosomeeggs, fewer effective drugs are directed to reverse the present hepatic fibrosis. Therefore, treatment targeting hepatic fibrosis associated with schistosomiasis remains a challenging proposition.The present study was designed to investigate the potential complementary schistosomicidal and hepatoprotective activities of the methanol extract ofCapparis spinosaL. (C. spinosa) with or without praziquantel (PZQ) and compare results with silymarin (Milk thistle), a known hepatoprotective and antifibrotic agent, on induced liver fibrosis by experimentalSchistosoma mansoni(S. mansoni) infection. Total polyphenols in the extract were determined using colorimetric assay.C. spinosaL. caused a partial decrease in worm burden; a statistically significant reduction in hepatic and intestinal tissue egg load, what was associated histopathologically with decreasing in both the number and diameter of granulomas, as well as restoring serum aminotransferases (AST & ALT), alkaline phosphatase (ALP) and improving liver albumin synthesis. The best results were obtained in the group of mice treated withC. spinosaL. and PZQ together. Quantitative estimation of total polyphenols content using colorimetric assay showed thatC. spinosaL. leaves contain higher concentration of polyphenolic compounds than fruits.It was concluded thatC. spinosaL. has a promising hepatoprotective and antifibrotic properties and could be introduced as a safe and effective therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis. Nevertheless further studies on the mechanism of action ofC. spinosaL. in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

Studies on the effects of cercarial concentration and length of exposure on the infection of mice by St Lucian Schistosoma mansoni cercariae in a natural running-water habitat

Parasitology ◽  
1974 ◽  
Vol 68 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Edward Suchart Upatham
Keyword(s):  
Schistosoma Mansoni ◽  
Infection Rate ◽  
Worm Burden ◽  
Running Waters ◽  
Direct Proportion ◽  
Infection Rates ◽  
Domestic Water ◽  
Running Water ◽  
Long Period ◽  
Water Washing

The effects of cercarial concentration and length of exposure on the infection of mice by St Lucian Schistosoma mansoni cercariae were investigated in a running-water habitat.For all exposure times, mice exposed to cercarial concentrations from 2·5 to 40 cercariae per mouse acquired no infections. At higher concentrations, infection rates and worm burdens of mice increased in direct proportion to cercarial concentrations and exposure times. The highest infection rate (57·9 %) and worm burden (46 worms) were obtained in mice exposed for 256 mm to 1280 cercariae per mouse.Cercarial concentrations are low in St Lucian running waters, a fact suggesting that the risk of persons becoming infected while fording, collecting domestic water, washing clothes and swimming in habitats with reasonable flows is very low. It appears that most infected individuals acquire a low worm burden over a rather long period of time.

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