Artesunate effect on schistosome thioredoxin glutathione reductase and cytochrome c peroxidase as new molecular targets in schistosoma mansoni-infected mice / 生物医学与环境科学（英文）

<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>

Artesunate effect on Schistosome thioredoxin glutathione reductase and cytochrome-C peroxidase as new molecular targets in Schistosoma mansoni infected mice

Schistosomiasis remains one of the most important parasitic diseases. Extensive use of praziquantel [PZQ] with concerns about possibility of drug resistance development, unavailability of an applicable vaccine, and absence of a reasonable alternative to PZQ, all represent a real challenge in control of schistosomiasis. Artemisinin derivatives are promising anti-schistosomal compounds, but their molecular mechanism of action on schistosomes is still not well defined. This study investigated the possible effect of artesunate [ART] on schistosome thioredoxin glutathione reductase [TGR] and cytochrome c peroxidase [CcP] in Schistosoma mansoni-infected mice. The animals used were divided into four groups. Group I: infected untreated group [control group]; group II: infected then treated with ART; group III: infected then treated with PZQ; and group IV: infected then treated with both ART and PZQ. ART was given orally in four doses, each of 300 mg/kg starting at 14th day post-infection [PI] and then every 2 weeks. PZQ was given orally in a single dose of 600 mg/kg at 42nd day PI. Then all mice were subjected to the following: adult S. mansoni worm count at 10 weeks PI, tissue egg count in liver and estimation of TGR and CcP mRNA expression in S. mansoni adult worms by semi-quantitative real time-PCR [rt-PCR]. Semi-quantitative rt-PCR values revealed that treatment with ART caused significant decrease in expression of schistosome TGR and CcP in contrast to PZQ which did not cause significant change in their expression. In addition, there was more reduction in total and female worm counts in ART-PZQ treated group than in other treated groups. 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. The current study elucidated for the first time that anti-schistosomal mechanism of action of ART is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, the addition of ART to PZQ could achieve complete cure outcome in treatment of schistosomiasis