Study On The Effect Of Artesunate Against Schistosoma Japonicum

Objective To study the changes of the reproductive system of Schistosoma japonium ,the morphology and histopathology alterations in adult worm and contents of DNA and protein,and changes of tritiated nucleoside uptake after treated with artesunate, in order to investigate the antischistosoma properties of artesunate and reveal its mechanisms.Methods: Mice infected with cercariae of Schistosoma japonicum were orally administered with artesunate in a single dose of 300mg/kg at 20d following the infection .The mice were sacrificed and perfused by the portal perfusion method for the recovery of worms three weeks after the administration. The changes of quantity of eggs produced by adult Schistosoma japonicum, the size of reproduction organ and the development of reproductive cell were investigated ; Mice infected with 33d Schistosoma japonicum were treated with the same dose of artesunate , then the mice were sacrificed and liver tissue sections were examined under a light microscope to invetigate the hepatic shift and artesunate-induced alterations in worm momphology and histopathology; mice were treated with one dose of artesunate at 300mg/kg 18d after infection,when the mice harboured juvenile S.japonicum.24h after treatment , mice were sacrificed and schistosomula were collected to determined DNA and protein contents (using ultraviolet ray- absorption and bradeford method,respectively),every ten schistosomula were maintained in drug-free medium containing 3H thymidine for 24h , the tritiated nucleoside uptake and incoration into nucleic acid were measured,using filter membrane and homogenate.Results: The main results are given as follows:(1) The quantity of eggs in the liver had significant difference in the administered group, as well as in vitro. The ovaries of female developed slowly in the administered group and had a smaller size than in the control group. There were more immature ovotid in ovaries. The major alterations observed in female S.japonicum ovary included more immature oocytes and less mature ones,which arrange rarefactively, shaped irregularly. The mature oocytes contain pallid satained cytolymph and indistinct chromatospherite, compared to features of the mormal ovary. The features of the testicle and vitellarium revealed no apparent alterations compared to the controled worms under light microscope .(2) The DNA and protein contents of schistosomula recovered from the host 24h after treatment were markedly decreased by 23.0% and 33.6%, respectively. When the above-mentioned schistosomula were in vitro exposed to the tritiated nucleoside for 24h, apparent decrease in tritiated nucleoside uptake with reducton of 61.1% was seen in the treated schistosomula. The incorporation of 3H thymidine into the schistosomula DNA 24h after co-incubation was reduced by 40.8%(3) Artesunate administration at a single oral dose of 300mg/kg to mice infected with 33d adult S.japonicum induced a hepatic shift with a slow onset. 24h after the mice were treated, 73.5% of the adult worms had shifted to the liver and increased to 89.3% 48h after treatment.The major changes in the adult worms included (1)focal roughening and swelling of the tegument. (2)adherence of inflawwatory cells to the damaged tegument, or even penetration into the worm body. (3)the intestinal canal was often filled with indigestive red cells and a hemoprotein mass. (4)pigment particles were released and distributed in the parenchymal tissues. All damaged worms were surrounded and infiltrated by numerous eosinophils predominated by inflammatory cells.Conclusions Artesunate can decrease the DNA and protien contents of schistosomula, and apparent decrease in tritiated nucleoside uptake and incorporation of 3HTDR into DNA was seen in schistosomula, can induce tegument damages,such as focal roughening and swelling of the tegument. Artesunate could inhibit the development of the ovaries of female ones, also could decrease or inhibit the egg production. It has effect on the reproduction of Schistosoma japonicum. Artesunate can mitigate the pathogenetic condition and control the spread of Schistosomiasis japonica.