Glutathione inhibits the antischistosomal activity of artemether.
OBJECTIVE
To observe the effect of reduced glutathione (GSH) and glutathione depleting agent 1-chloro-2,4-dinitrobenzene (CDNB) on the susceptibility of adult Schistosoma japonicum to artemether (Art) in combination with hemin in vitro.


METHODS
In vitro, malondialdehyde(MDA) levels were determined in five-week-old worms incubated without or with Art, hemin, GSH, and CDNB, either alone or in combination, for 24 h, and the remaining worms were continuously incubated up to 96 h for worm survival assessment. In vivo, GSH levels were determined in worms freshly recovered from mice 6, 12 and 24 h after treatment with Art 300 mg/kg.


RESULTS
In vitro, GSH decreased the proportion of worms killed by Art plus hemin, but CDNB rendered the worms susceptible to the killing. The above-mentioned distinguishing features of GSH and CDNB were associated with their reverse effect on worm lipid peroxidation induced by Art-hemin system. In vivo, Art led to a slight decrease followed by a significant increase in the parasite GSH levels.


CONCLUSIONS
GSH might play an important role in the defense of the worms against Art-generated toxic peroxides and free radicals.
Zhai
Zi-li
ZL
Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai 200025.
Jiao
Pei-ying
PY
Mei
Jing-yan
JY
Xiao
Shu-hua
SH
D000818:Animals; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology*; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D011817:Rabbits; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000378:metabolism; D012556:Schistosomicides / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*
D037621:Artemisinins; D004137:Dinitrochlorobenzene; D012556:Schistosomicides; D012717:Sesquiterpenes; D008315:Malondialdehyde; D006427:Hemin; D000077549:Artemether; D005978:Glutathione