Increase in neutrophil count after repeated exposure of Plasmodium berghei-infected mice to artemisinin

Main Article Content

Lilik Maslachah
Rahmi Sugihartuti

Abstract

Background
Leukocytes play an important role in the elimination of malaria infection. The leukocyte profile upon elimination of the malaria parasites that have been exposed to antimalarials and are subsequently capable of faster growth has not been researched. The aim of this research was to evaluate the role of mouse leukocytes in the elimination of parasites as shown by the leukocyte profile.

Methods
An experimental research with post test only control group design was conducted involving 24 male mice of the Swiss Albino strain weighing 20 g -30 g, and 2.5 months old. They were randomized into four groups: two control groups (K1, KP) and two treatment groups (P1, P4). Artemisinin at a dose of 0.04 mg/g body weight was given to the mice for 3 days, starting 2 days after infection. The leukocyte profile was observed on the 2nd, 5th, 8th, and 10th day after infection. The results were analyzed by two-way Anova.

Results
As shown in treatment control group KP and treatment group P4, P. berghei that had been passaged in the mice and were still viable after repeated exposure to artemisinin, may cause changes in leukocyte profile. On the 10th day of infection, the neutrophil percentage in group P1 showed a significantly different decrease when compared with the other groups (K1, KP and P4) (p<0.05).

Conclusion
Repeated exposure to artemisinin of mice infected with P. berghei can cause changes in neutrophil profile in mice.

Article Details

How to Cite
Maslachah, L., & Sugihartuti, R. (2017). Increase in neutrophil count after repeated exposure of Plasmodium berghei-infected mice to artemisinin. Universa Medicina, 36(1), 49–58. https://doi.org/10.18051/UnivMed.2017.v36.49-58
Section
Original Articles
Author Biography

Lilik Maslachah, Veterinary Pharmacy Laboratory, Department of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Airlanggga University

Departemen Kedokteran Dasar Veteriner

References

World Health Organization. WHO global malaria programme: world malaria report 2015. Geneva: World Health Organization;2015.

Afonso A, Hunt P, Cheesman S, et al. Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase) tctp, mdr1 and cg10. Antimicrob Agents Chemother 2006; 50:480-9.

Noedl H. Evidence of artemisinin resisntant malaria in Western Cambodia. N Engl J Med 2008;359:2619-620.

Wongsrichanalai C, Meshnick SR. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia-Thailand border. Emerg Infect Dis 2008;4:716-8.

Maslachah L, Dachlan YP, Nidom CA, et al. Profil fenotipik Plasmodium falciparum galur Papua 2300 akibat paparan antimalaria artemisinin in vitro. MKB 2015;47:1-9.

Paloque L, Ramadani AP, Mercereau-Puijalon O, et al. Plasmodium falciparum: multi faceted resistance to artemisinins. Malar J 2016;15:149. DOI: 10.1186/s12936-016-1206-9.

Njokah MJ, Kang JN, Kinyua J, et al. In vitro selection of Plasmodium falciparum Pfcrt and Pfmdr1 variants by artemisinin. Malar J 2016;15:381. doi: 10.1186/s12936-016-1443-y.

Craig AG, Grau GE, Janse C, et al. The role of animal models for research on severe malaria. PLoS Pathogens 2012;8:2 e1002401.

Darlina, Raharjo T, Nurhayati S. Changes of leukocytes type in mice immunized with irradiated Plasmodium berghei. National Seminar, 16 November,Yogyakarta;2011.

Darlina, Krisnanto T, Fauzan A. Haematopoietic response of mice infected with erythrocytic stadium of gamma irradiated Plasmodium berghei. Indonesian J Nuclear Sci Technol 2012; 13:85-94.

Clemmer L, Martin YC, Zanini GM, et al. Artemether and artesunate show the highest efficacies in rescuing mice with late stage cerebral malaria and rapidly decrease leukocyte accumulation in brain. Antimicrob Agents Chemother 2011;55:1383-90.

Kiboi DM, Irungu BN, Langat B, et al. Plasmodium berghei ANKA: selection of 1. World Health Organization. WHO global malaria programme: world malaria report 2015. Geneva: World Health Organization;2015.

Afonso A, Hunt P, Cheesman S, et al. Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase) tctp, mdr1 and cg10. Antimicrob Agents Chemother 2006; 50:480-9.

Noedl H. Evidence of artemisinin resisntant malaria in Western Cambodia. N Engl J Med 2008;359:2619-620.

Wongsrichanalai C, Meshnick SR. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia-Thailand border. Emerg Infect Dis 2008;4:716-8.

Maslachah L, Dachlan YP, Nidom CA, et al. Profil fenotipik Plasmodium falciparum galur Papua 2300 akibat paparan antimalaria artemisinin in vitro. MKB 2015;47:1-9.

Paloque L, Ramadani AP, Mercereau-Puijalon O, et al. Plasmodium falciparum: multi faceted resistance to artemisinins. Malar J 2016;15:149. DOI: 10.1186/s12936-016-1206-9.

Njokah MJ, Kang JN, Kinyua J, et al. In vitro selection of Plasmodium falciparum Pfcrt and Pfmdr1 variants by artemisinin. Malar J 2016;15:381. doi: 10.1186/s12936-016-1443-y.

Craig AG, Grau GE, Janse C, et al. The role of animal models for research on severe malaria. PLoS Pathogens 2012;8:2 e1002401.

Darlina, Raharjo T, Nurhayati S. Changes of leukocytes type in mice immunized with irradiated Plasmodium berghei. National Seminar, 16 November,Yogyakarta;2011.

Darlina, Krisnanto T, Fauzan A. Haematopoietic response of mice infected with erythrocytic stadium of gamma irradiated Plasmodium berghei. Indonesian J Nuclear Sci Technol 2012; 13:85-94.

Clemmer L, Martin YC, Zanini GM, et al. Artemether and artesunate show the highest efficacies in rescuing mice with late stage cerebral malaria and rapidly decrease leukocyte accumulation in brain. Antimicrob Agents Chemother 2011;55:1383-90.

Kiboi DM, Irungu BN, Langat B, et al. Plasmodium berghei ANKA: selection of resistance to piperaquine and lumefantrine in a mouse model. Exp Parasitol 2009;122: 196-202.

Henriques G, Martinelli A, Rodrigues L, et al. Artemisinin resistance in rodent malaria–mutation in the AP2 adaptor ì-chain suggest involvement of endocytosis and membrane protein trafficking. Mal J 2013;12:118.

Odeghe OB, Uwakwe AA, Monago CC. Some biochemical and haematological studies on the methanolic extract of Anthocleista grandiflora stem bark. Int J Appl Sci Technol 2012;2:58-65.

Baratawidjaja KG, Rengganis I, editors. Imunologi dasar. Edisi ke 9. Jakarta: Balai Penerbit Fakultas Kedokteran Universitas Indonesia;2010.

Onwuamah CK, Phillip UA, Odeigah PG. Mouse mortality from a high plasmodium berghei inoculum density may be due to immune suppression in the host. Int J Med Med Sci 2010; 2:162-6.

Maslachah L. Efek paparan artemisinin berulang terhadap perkembangan Plasmodium falciparum resisten in vitro [Disertasi]. Surabaya; Universitas Airlangga;2013.

Teuscher F, Chen N, Kyle DE, et al. Phenotypic changes in artemisinin resistant Plasmodium falciparum line in vitro: Evidence for decreased sensitivity to dormancy and growth inhibition. Antimicrob Agent Chemother 2012;56:428-31.

Fabre V, Beiting DP, Bliss SK, et al. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 2009; 182:1577-83.

Balogun EA, Adebayo JO, Zailani AH, et al. Activity of ethanolic extract of Clerodendrum violaceum leaves against Plasmodium berghei in mice. Agric Biol J N Am 2009;1:307-12.

Anggraini R, Widodo GP, Ningsih D. Antiplasmodium effect of Mundu (Garcinia dulcis Kurz) cortex N hexane extract with leukocyte and hemoglobin amount parameter on Swiss Webster mouse infected with Plasmodium berghei. Indonesian Pharmacy J 2011;8:45-52.