Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

Aly, Ibrahim; Hendawy, Mohamed; Ali, Eman; Nosseir, M. H.

doi:10.1590/s0074-02762010000600001

Cited by 23 publications

(11 citation statements)

References 41 publications

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“…Previous studies regarding drug resistance, have already presented evidence of an increased tolerance to PZQ in male worms [ 19 , 21 , 22 , 36 , 37 , 46 ]. It should be noted that when using in vivo and ex vivo assays the interaction between the effects caused by the drug and those caused by the host immune system on the parasite are not taken in consideration [ 33 , 47 , 48 ]. In conclusion, our work describes for the first time, the application of a successful methodology previously applied in bacteria and cancer cells, using the universal efflux pump substrate EtBr, for the evaluation of drug transporter systems on S .…”

Section: Discussionmentioning

confidence: 99%

The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

Pinto-Almeida¹,

Mendes

Armada

et al. 2015

PLoS ONE

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BackgroundSchistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug.Methodology/Principal FindingsHere we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR.Conclusions/SignificanceThis work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni.

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Section: Discussionmentioning

confidence: 99%

The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

Pinto-Almeida¹,

Mendes

Armada

et al. 2015

PLoS ONE

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“…Measurement of mean granuloma diameter was performed using an ocular micrometer at magnification of 100x. Only nonconfluent, lobular granulomas containing eggs in their centers were measured (periocular granulomas) [34]. …”

Section: Experimental Designmentioning

confidence: 99%

Comparative Evaluation of Anthelmintic Activity of Edible and Ornamental Pomegranate Ethanolic Extracts againstSchistosoma mansoni

Yones

Badary

Sayed

et al. 2016

BioMed Research International

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Due to the development of praziquantel (PZQ) schistosomes resistant strains, the discovery of new antischistosomal agents is of high priority in research. This work reported the in vitro and in vivo effects of the edible and ornamental pomegranate extracts against Schistosoma mansoni. Leaves and stem bark ethanolic extracts of both dried pomegranates were prepared at 100, 300, and 500 μg/mL for in vitro and 600 and 800 mg/kg for in vivo. Adult worms Schistosoma mansoni in RPMI-1640 medium for in vitro and S. mansoni infected mice for in vivo tests were obtained from Theodor Bilharz Research Institute, Cairo, Egypt. In vitro activity was manifested by significant coupled worms separation, reduction of motor activity, lethality, and ultrastructural tegumental alterations in adult worms. In vivo activity was manifested revealed by significant reduction of hepatic granulomas number and diameter, decreased number of bilharzial eggs in liver tissues, lowered liver inflammatory infiltration, decreased hepatic fibrosis, and inducible nitric oxide synthase (iNOS) expression. Ethanolic stem bark extract of edible pomegranate exhibited highest antischistosomal activities both in vitro and in vivo. Therefore, pomegranate showed a good potential to be used as a promising new candidate for the development of new schistosomicidal agents.

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“…(Rothenberg et al 2003) Schistosomiasis might be associated with an imbalance in Th1/Th2 cytokine, with a shift toward the Th2 system (Acosta et al 2002). Some studies about cytokine alteration such as IFN-γ showed a different trend (Aly et al 2010); due to lack of consistency of results, this meta-analysis aims to verify whether the different cytokine imbalances were substantiated by evidence.…”

Section: Introductionmentioning

confidence: 97%

Inflammatory cytokines IFN-γ, IL-4, IL-13 and TNF-α alterations in schistosomiasis: a meta-analysis

Sun

Yang

et al. 2011

Parasitol Res

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Cytokines play an important role in the immunological pathogenesis of schistosomiasis. Schistosomiasis would be associated with an imbalance in inflammatory cytokines that leads to a decrease of T helper (Th) 1 and an increase of Th2 cytokine secretion. Corresponding data so far have been inconsistent, so we performed a meta-analysis to assess whether cytokine alterations were risk factors for schistosomiasis progression. We searched MEDLINE, EMBASE, and CNKI databases for literatures including abstracts, reviews, and reference lists. Our studies included assessment of cytokine concentrations in vivo plasma or serum and secretion of cytokines in vitro by peripheral blood leukocytes from schistosomiasis patients or infected individuals with schistosome. The prototypic Th1 and Th2 cytokines IFN-γ and interleukin (IL)-4 were assessed as well as IL-13 and tumor necrosis factor-alpha (TNF-α). The results implied that an increase occurs in TNF-α and IL-4 with schistosomiasis progression.

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Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

Cited by 23 publications

References 41 publications

The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

Comparative Evaluation of Anthelmintic Activity of Edible and Ornamental Pomegranate Ethanolic Extracts againstSchistosoma mansoni

Inflammatory cytokines IFN-γ, IL-4, IL-13 and TNF-α alterations in schistosomiasis: a meta-analysis

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