Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum

  • 207 Accesses

  • 23 Citations

Abstract

Artemether and artesunate, derivatives of the antimalarial artemisinin, as well as their main metabolite, dihydroartemisinin, all exhibit antischistosomal activities. The purpose of the current study was to compare the effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum. We carried out experiments with mice, infected with 40 cercariae of S. japonicum, and treated with artemether, aretesunate and dihydroartemisinin (all at a single dose of 300 mg/kg, and the dose of the mixed three drugs is also 300 mg/kg) at multiple doses or combination therapy on days 6–8 or 34–36 post-infection. Administration with artemether, artesunate or dihydroartemisinin for 3 successive days reduced total worm burdens by 79.5−86% (30.86 ± 4.98 of mean total worm burden in control), female worm burdens by 79.4−86.7% (11.29 ± 2.63 of mean female worm burden in control) (all P values <0.01 vs. control), depending on different treatment protocols given on days 6–8 post-infection. However, no differences were seen between each treatment group (all P > 0.05). While the same treatment was given on days 34–36 post-infection, total worm burden reductions of 73.8−75.8% were achieved (29.44 ± 3.36 of mean total worm burden in control), which were significant when compared with the untreated control group (all P values <0.01). In all different treatment groups, female worm reductions (ranging from 88.7% to 93.1%, while the mean female worm burden in control is 10.33 ± 1.80) were consistently higher than the total worm reductions, resulting always in significantly lower female worm burdens when compared to the corresponding control (all P values < 0.01). However, there were no significant differences found between each treatment group (all P values >0.05). It is concluded that artemether, artesunate and dihydroartemisinin can be used to control schistosomiasis japonica, as a strategy to prevent S. japonicum infection. Administration with artemether, artesunate and dihydroartemisinin at multiple doses or in combined treatment damages both juvenile and adult S. japonicum, without statistically significant differences among the three drugs at the same dose.

This is a preview of subscription content, log in to check access.

References

  1. Abdul-Ghani RA, Loutfy N, Hassan A (2009) Experimentally promising antischistosomal drugs: a review of some drug candidates not reaching the clinical use. Parasitol Res 105:899–906

  2. Abdul-Ghani R, Loutfy N, Sheta M, Hassan A (2011) Artemether shows promising female schistosomicidal and ovicidal effects on the Egyptian strain of Schistosoma mansoni after maturity of infection. Parasitol Res 108:1199–1205

  3. Cioli D, Pica-Mattoccia L (2003) Praziquantel. Parasitol Res 90:S3–S9

  4. Cioli D, Valle C, Angelucci F, Miele AE (2008) Will new antischistosomal drugs finally emerge? Trends Parasitol 24:379–382

  5. Doenhoff MJ, Cioli D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21:659–667

  6. Haynes RK, Chan WC, Wong HN, Li KY, Wu WK, Fan KM, Sung HH, Williams ID, Prosperi D, Melato S, Coqhi P, Monti D (2010) Facile oxidation of leucomethylene blue and dihydroflavins by artemisinins: relationship with flavoenzyme function and antimalarial mechanism of action. ChemMedChem 5:1282–1299

  7. Hua HY, Liang YS, Zhang Y, Wei JF, Guo HX (2010) The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China. Parasitol Res 107:873–878

  8. Li HJ, Wang W, Qu GL, Tao YH, Xing YT, Li YZ, Wei JY, Dai JR, Liang YS (2011) In-vivo activity of dihydroartemisinin against Schistosoma japonicum. Ann Trop Med Parasitol 105:181–185

  9. Magalhães LG, Machado CB, Morais ER, Moreira EB, Soares CS, da Silva SH, Da Silva Filho AA, Rodrigues V (2009) In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res 104:1197–1201

  10. Magalhães LG, Kapadia GJ, da Silva Tonuci LR, Caixeta SC, Parreira NA, Rodrigues V, Da Silva Filho AA (2010) In vitro schistosomicidal effects of some phloroglucinol derivatives from Dryopteris species against Schistosoma mansoni adult worms. Parasitol Res 106:395–401

  11. McIntosh HM, Olliaro P (2001) Artemisinin derivatives for treating severe malaria (Cochrane Review). In: The Cochrane Libarary, 1. Oxford: Update Software.

  12. Meshnick SR, Tsang TW, Lin FB, Pan HZ, Chang CN, Kuypers F, Chiu D, Lubin B (1989) Activated oxygen mediates the antimalarial activity of qinghaosu. Prog Clin Biol Res 313:95–104

  13. Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LCC (2006) Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99:505–521

  14. Shaohong L, Kumagai T, Qinghua A, Xiaolan Y, Ohmae H, Yabu Y, Siwen L, Liyong W, Maruyama H, Ohta N (2006) Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols. Parasitol Int 55:63–68

  15. Utzinger J, Chollet J, Tu Z, Xiao S, Tanner M (2002) Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice. Trans R Soc Trop Med Hyg 96:318–323

  16. WHO (2002) Controlling disease due to helminth infections. WHO Technical Report Series No. 912. Geneva, Switzerland.

  17. Xiao SH (2005) Development of antischistosomal drugs in China, with particular consideration to praziquantel and the artemisinins. Acta Trop 96:153–167

  18. Xiao SH, You JQ, Gao HF et al (2002) Schistosoma japonicum: effect of artemether on glutathione S-transferase and superoxide dismutase. Exp Parasitol 102:38–45

  19. Xiao SH, Mei JY, Jiao PY (2009) The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum. Parasitol Res 106:237–246

  20. Xiao SH, Keiser J, Chen MG, Tanner M, Utzinger J (2010) Research and development of antischistosomal drugs in the People's Republic of China a 60-year review. Adv Parasitol 73:231–295

  21. Xiao SH, Mei JY, Jiao PY (2011) Effect of mefloquine administered orally at single, multiple, or combined with artemether, artesunate, or praziquantel in treatment of mice infected with Schistosoma japonicum. Parasitol Res 108:399–406

  22. Zhai ZL, Jiao PY, Mei JY, Xiao SH (2002) Glutathione inhibits the antischistosomal activity of artemether. Chin J Parasitol Parasit Dis 20:212–215

Download references

Acknowledgements

This study received financial support from the National Science & Technology Pillar Program of China (Grant no. 2009BAI78B06), and Jiangsu Department of Health (Grant no. X200911). The experiments in this study are in compliance with the current laws and regulations of China.

Author information

Correspondence to Jian-Rong Dai or You-Sheng Liang.

Additional information

H.-J. Li and W. Wang contributed equally to this work and should be considered co-first authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, H., Wang, W., Li, Y. et al. Effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum . Parasitol Res 109, 515–519 (2011). https://doi.org/10.1007/s00436-011-2474-5

Download citation

Keywords

  • Artemisinin
  • Adult Worm
  • Praziquantel
  • Artesunate
  • Worm Burden