Haematological and Histopathological Effects of Artemisinin-Based Combination Therapy in Healthy Mice

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Ukamaka Elizabeth Okafor
Asolo Chioma Helen
Ogonna Daniel Nwankwo


Artemisinin-based combination therapy had been recommended for the treatment of uncomplicated malaria in Africa.      

Aim: This study investigated the effects of artesunate/amodiaquine (A/A) and dihydroartemisinin/ piperaquine (D/P) on some blood parameters and histopathology of the liver and kidney of mice.

Materials and Methods: A Complete randomized design was applied. Fifty mice were randomly assigned to five treatment groups of ten animals each. Therapeutic doses of the drugs were orally administered to the animals. Group A received normal saline (control), group B received 10/14mg/kg body weight of artesunate/amodiaquine for 3 days, group C received 10/18mg/kg of dihydroartemisinin/piperaquine for 3 days, group D received similar treatment with group B, but were followed up to 28 days, group E received similar treatment with group C but were also followed up to 28 days. After experimental period, blood samples were collected for determination   of white blood cell count, white blood cell differential count, red blood cell count, packed cell volume and haemoglobin concentration. Liver and kidney were also harvested for histopathological analysis.

Results: Result showed that therapeutic doses of artesunate/amodiaquine and dihydroaretmisinin/ piperaquine had no significant (P>0.05) effects on heamatological parameters accessed. Mild inflammation and degeneration of hepatocyte were observed in the liver of the group treated with D/P while fatty change was found in the group treated with A/A.  Venous congestion was observed in the kidney of the group treated with D/P. After 28 days, degeneration of hepatocyte and inflammatory cells were observed in the liver. Shrunken glomerulus was found in the kidney of the group treated with D/P.

Conclusion: These drugs are detrimental to the liver and kidney even at therapeutic dose therefore, they should be used with caution.

Artemisinin, dihydroartemisinin, piperaquine, malaria, artesunate, amodiaqine, antimalaria

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How to Cite
Okafor, U. E., Helen, A. C., & Nwankwo, O. D. (2020). Haematological and Histopathological Effects of Artemisinin-Based Combination Therapy in Healthy Mice. Asian Journal of Biology, 10(1), 29-37. https://doi.org/10.9734/ajob/2020/v10i130097
Original Research Article


World Health Organization. World malaria report, 2015. WHO, Geneva

World Health Organization. World Malaria Report, 2017. WHO, Geneva

Obianime, AW, Aprioku JS. Mechanism of action of arteminins on biochemical hematological and reproductive parameters in male guinea pig. International Journal of Pharmacology. 2011;7(1):84-95.

World Health Organisation. A background document for the WHO global strategy for containment of antimicrobial resistance, 2001. WHO, Geneva

Qinghaosu Antimalaria Coordinating Research Group. Antimalaria studies on Qinghaosu. Chinese Medical Journal, 1979;92(12):811–816.

Ashton M, Sy ND, Van Huong N. Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clinical Pharmacology and Therapeutics.1998;63(4):482–493.

Li QP, Weina J, Milhous WK. (2007). Pharmacokinetic and pharmacodynamic profiles of rapid-acting artemisinins in the antimalarial therapy. Current Drug Therapy. 2007;2(3):210–223.

Klayman DL. Qinghaosu (artemisinin): An antimalarial drug from China. Science. 1985;228 (4703):1049–1055.

Price RN, Van vugt M, Nosten F, Luxemburger C, Brockman A, Phaipun I, et al. Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria. American Journal of Tropical Medicine and Hygeine. 1998;59:883–888.

Mclintosh HM, Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of systematic Review. 2000;(2):256-265

World Health Organisation. Guidelines for treatment of malaria, 2006. WHO, Geneva.

Olliaro PL, Taylor W. Developing artemisinin treatment drug resistance falciparum malaria. Journal of postgraduate Medicine. 2004;(50):40-44.

Merck I. An encyclopedia of chemicals, drugs and biological. USA; Rahway NJ; 1983.

Tarning J, Lindegardh N, Sandberg S, Day NJ, White NJ, Ashton M. Pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat. Journal of Pharmaceutical Sciences. 2008;(97):3400–3410.

World Health Organisation. World Malaria Report; 2010. WHO, Geneva.

Hatton CS, Peto TE, Bunch C, Pasvol G, Russell SJ, Singer CR et al.The frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria. Lancet. 1986;(1):411-414

World Health Organisation. World Health Organisation model list of essential medicines; 2019. WHO, Geneva. Hdl:10665/325771

Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF. Piperaquine: a resurgent antimalarial drug. Drugs. 2005;65(1):75-87.

Olayinka ET, Ore A. Alterations in Antioxidant Status and Biochemical Indices Following Administration of Dihydroartemisinin-Piperaquine Phosphate (P-ALAXIN®. Journal of Pharmacy and Biological Sciences. 2013;5(4):43-53.

Baker FJ, Silverton RE, Pallistea CJ. Introduction to Medical Laboratory Technology. Nigeria: Bouty press; 1998.

Dacie SJV, Lewis SM. Practical Haematology. Edinburgh: Churchil Livingstone; 1984.

Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. Edinburgh: Churchill Livingstone; 2002.

David FS. Transfusion Medicine Reviews. 1993;7(4):268-274

Agomo, UP, Merimikwu MM, Ismaila MW, Omalu IT, Oguche VI, Odey S. Efficacy, Safety, and Tolerability of Plasmodium falciparum Malaria in four geographical zones of Nigeria. Malaria Journal. 2008;7:172.

Omotosho, OO, Mutiu AA, Oyeyemi MO. Comparative Study of the Haematology and Serum Biochemistry of Male Wistar Rats Treated with Chloroquine and Artesunate. Journal of Physiology and Pharmacology Advances. 2014;4(8):413-419.

Kareem F, Ifabunmi A, Osonuga O, Mutiu A, Alabi E, Ajani O. Haematological Changes Associated with Administration of Therapeutic dose of P-Alaxin in Healthy Adult Wistar Rats. Journal of Natural Sciences Research. 2014;4:20.

Orrel C, Taylor WR, Olliaro P. Acute asymptomatic hepatitis in a healthy normal volunteer exposed to oral doses of amodiaquine and Artesunate. Transaction of Royal Society Tropical Medicine and Hygiene. 2001;95:517-518.

Nwanjo HU, Oze G. Acute Hepatotoxicity Following Administration of Artesunate in Guinea pigs. Internet Journal of Toxicology. 2007;4:1-8.

Al-Ani IA, Al-Janabi ST, Hamoudi SR. Effect of some antimalaria drugs on the liver, biochemical and histopathological studies. International malaria symposium. 2013;1-17.

Aashish P, Tarun S, Pallavi B. Drug-induced Hepatotoxicity: A Review. Journal of Applied Pharmaceutical Science. 2012;2(5):233-243. DOI: 10 7324/japs.2012.2541

Bartoli E. Adverse effects of drugs on the kidney. European Journal of Internal Medicine. 2016;28:1-8.

Amaza DS, Momoh M, Zirahei1 JV, Rufai1 AA, Sambo N, Amos L et al. Effect of Oral Administration of Artesunate on the Histology of the Kidney in Albino Rat. Journal of Dental and Medical Sciences. 2013;3(5):15-20.

Barsoun RS. Malaria nephropathies. Nephrology Dialysis Transplant. 1998;13:1588-97.