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Glutathione inhibits the antischistosomal activity of artemether
Zi-li Zhai1, Pei-ying Jiao, Jing-yan Mei
1Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai 200025.
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.
Conclusion:
GSH might play an important role in the defense of the worms against Art-generated toxic peroxides and free radicals.