title: [Toxicity of several drugs against Schistosoma japonicum adult worms in vitro].
abstract: OBJECTIVE
  To observe the toxicity of auranofin, cisplatin, adriamycin, compounds 4N, H, B, O against Schistosoma japonicum adult worms in vitro and their inhibition on thioredoxin glutathione reductase (TGR).
  
  
  METHODS
  The drugs mentioned above with different concentrations were added into RPMI 1640 medium with Schistosoma japonicum adult worms, which had been cultured for 30 - 60 min. The activity, morphological changes and death situation of the worms were observed after 1, 6, 24, 48 h and 72 h, respectively, then the worms were transferred to fresh medium without drugs to observe whether their activity would be recovered, and 50% lethal dose (LD50) of the drugs against adult worms was determined. The TrxR and GR activities of thioredoxin glutathione reductase of Schistosoma japonicum in homogenized supernatant of adult worms processed by drugs were tested following the DTNB reduction and NADPH oxidation methods.
  
  
  RESULTS
  The mortality rates of 5 microg/ml of auranofin treating for 24 h, 20 microg/ml of 4N treating for 72 h, 60 microg/ml of H treating for 72 h, and 80 microg/ml of cisplatin treating for 72 h on adult worms were 100%, 60%, 66.7% and 100%, respectively, and there were statistically significant differences compared with the negative control group. LD50(s) of auranofin, 4N, H and cisplatin were 2.56, 17.59, 54.14 microg/ml and 52.87 microg/ml, respectively, but no toxic effects of other drugs on schistosome worms were found. The toxic effects of auranofin, 4N, cisplatin and H on adult worms were irreversible. Auranofin and cisplatin inhibited TGR activity of Schistosoma japonicum, but other drugs had no similar effect. 5 - 30 microg/ml of auranofin, 20 - 30 microg/ml of 4N, 70 - 150 g/ml of cisplatin, and 60 - 220 microg/ml of H caused the morphological changes of the worms after treating for 24 h.
  
  
  CONCLUSIONS
  Auranofin, cisplatin and compounds 4N and H have toxicity on Schistosoma japonicum adult worms in vitro, and the schistosomicidal effect of auranofin and cisplatin may be related to the inhibition of TGR activity.
authors.affiliation: Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Wuxi 214064, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Song
authors.forename: Chuan-Xin
authors.initials: CX
authors.lastname: Yu
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Zeng
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Qian
authors.forename: Xu-Ren
authors.initials: XR
authors.lastname: Yin
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Wan-Quan
authors.initials: WQ
authors.lastname: Hua
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001310:Auranofin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D015801:Helminth Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012549:Schistosoma japonicum / Q000033:anatomy & histology / Q000187:drug effects*; D012554:Schistosomiasis japonica / Q000469:parasitology; D012556:Schistosomicides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015801:Helminth Proteins; D009097:Multienzyme Complexes; D012556:Schistosomicides; D001310:Auranofin; D004317:Doxorubicin; D009247:NADH, NADPH Oxidoreductases; C466433:thioredoxin glutathione reductase; D002945:Cisplatin