title: Schistosoma mansoni: N-acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice.
abstract: Artemether (Art), a derivative of the antimalarial artemisinin, also exhibit antischistosomal properties. N-acetylcysteine (NAC) has a diversity of applications, largely because of the chemical properties of the thiol moiety present in its structure. The ability of this moiety to sweep reactive oxygen species is well-established with NAC. This study investigates the ability of NAC to enhance the therapeutic potential of Art against adult Schistosoma mansoni infection and evaluates the protective role of this antioxidant on S. mansoni-induced oxidative stress. Mice were divided into five groups; normal (i), infected control (ii), infected treated with NAC, 300mg/kg 5 days a week/4weeks (iii), infected treated with Art (300mg/kg) 7 weeks post infection (iv) and infected treated with both NAC and Art (v). Results showed that Art produced a significant reduction in total number of worms when used alone. Also, it decreased hepatic ova count significantly accompanied with an increase in the percentage of dead ova. Treatment with NAC alone increased the percentage of dead ova; meanwhile, it enhanced the decrease in total number of worms and hepatic ova count when used with Art. Infection with S. mansoni significantly increased tissue GSH, GR, SOD and serum ALT and GGT, while decreased the activities of GST, GPx and the levels of proteins and albumin compared to normal control. Treatment with NAC alone approximately recovered the contents of GSH, activities of GPx and levels of serum albumin, ALT and GGT relative to normal control. A tendency for normalization in activities of the antioxidant enzymes mentioned above and serum levels of liver function tests was observed in the groups treated with Art alone or Art+NAC.
  
  
  CONCLUSIONS
  NAC downregulates oxidative stress induced by S. mansoni infection and enhances the therapeutic potential of artemether against adult schistosomes.
authors.affiliation: Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt. sayedseifeldin@yahoo.com
authors.forename: Sayed H
authors.initials: SH
authors.lastname: Seif el-Din
authors.forename: Amir M
authors.initials: AM
authors.lastname: Al-Hroob
authors.forename: Fatma A
authors.initials: FA
authors.lastname: Ebeid
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology / Q000469:parasitology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000378:metabolism; D012556:Schistosomicides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D037621:Artemisinins; D016166:Free Radical Scavengers; D012556:Schistosomicides; D000077549:Artemether; D000111:Acetylcysteine