Schistosoma japonicum: effect of artemether on glutathione S-transferase and superoxide dismutase.
Glutathione S-transferase (GST) and superoxide dismutase (SOD) are major antioxidant enzymes of schistosomes that are involved in detoxification processes. To study the effect of artemether on these enzymes, mice infected with adult Schistosoma japonicum, were treated with artemether either at a subcurative (100 mg/kg) or a curative dose (300 mg/kg). Schistosomes were recovered 24-72 h post-treatment separated by sex and used for GST and SOD activity measurements. Female worms showed consistently higher GST inhibitions than males. For instance, 24 h after administration of 100 mg/kg artemether, GST activities of female worms were inhibited by 23.3%, as compared to 12.7% in males. Both activities were significantly lower when compared to worms recovered from untreated mice. Slightly higher inhibitions were observed at the higher dose of artemether, which gradually increased to levels of 52.5-55.1%, 72 h post-treatment. GST inhibitions could be reversed by application of 1,4-dithiothreitol at a concentration of 10 mmol/L. Adding L-cysteine also reduced GST inhibitions, but in female worms, GST activities remained significantly higher than in worms from untreated animals. Administration of 300 mg/kg artemether resulted in significant reductions of SOD activities in both sexes. In conclusion, these results suggest that the inhibition of GST and, to a lesser extent also SOD enzymes, could lead to increased schistosome susceptibility to oxidant attacks and might be linked with the antischistosomal action of artemether.
Xiao
Shu-Hua
SH
Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, Shanghai 200025, PR China.
You
Ji-Qing
JQ
Gao
Hui-Fang
HF
Mei
Jin-Yan
JY
Jiao
Pei-Ying
PY
Chollet
Jacques
J
Tanner
Marcel
M
Utzinger
Jürg
J
D000818:Animals; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000201:enzymology; D012554:Schistosomiasis japonica / Q000188:drug therapy / Q000201:enzymology / Q000469:parasitology; D012556:Schistosomicides / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D000077549:Artemether; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D003545:Cysteine; D004229:Dithiothreitol