ABSTRACT
To explore the structure and function of thioredoxin glutathione reductase (TGR) from Schistosoma j aponi-cum ,the homologous model of TGR in Schistosoma j aponicum was constructed by Swiss-Pdbviewer based on sequence and structure alignment .The potential substrates binding sites of TGR were analyzed and these sites of various TGRs were also as-sessed .Our results showed that the homologous model of Schistosoma japonicum TGR based on Schistosoma mansoni TGR structure was proved to be reasonable by PROCHECK program .Analysis of binding sites showed that NADPH and GDS bind-ing sites were conservative sites and GSH binding site was a specific site for parasite .Our data suggested that inhibitors which work in NADPH and GDS binding sites of other various TGRs may also interact with TGR form Schistosoma j aponicum .GSH binding region might be one of the potential targets for design of specific inhibitors of parasite TGRs .In addition ,C-terminal of TGR plays an important role in electron transfer and may participate in the binding of the substrate .Thus compound inhibiting swing of C-terminal could effectively restrain Schistosoma j aponicum TGR activity .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice.</p><p><b>METHODS</b>A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III: infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in S. mansoni adult worms by semi-quantitative rt-PCR.</p><p><b>RESULTS</b>Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZQ. Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups.</p><p><b>CONCLUSION</b>The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.</p>