1.Artesunate effect on schistosome thioredoxin glutathione reductase and cytochrome c peroxidase as new molecular targets in schistosoma mansoni-infected mice.
Amany A ABDIN ; Dalia S ASHOUR ; Zeinab S SHOHEIB
Biomedical and Environmental Sciences 2013;26(12):953-961
OBJECTIVETo investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice.
METHODSA 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.
RESULTSSemi-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.
CONCLUSIONThe 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.
Animals ; Artemisinins ; pharmacology ; Cytochrome-c Peroxidase ; drug effects ; genetics ; Male ; Mice ; Multienzyme Complexes ; drug effects ; genetics ; NADH, NADPH Oxidoreductases ; drug effects ; genetics ; Polymerase Chain Reaction ; RNA, Messenger ; genetics ; Schistosoma ; drug effects ; enzymology