Nephrotoxicity of Therapeutic Dose of Dihydroartemisinin-Piperaquine Phosphate in Male and Female Animals

Mutiu Adewunmi Alabi, Fatai A. Kareem, Fatai Akinwunmi3, Ayodeji O. Obatoye


Dihydroartemisinin-piperaquine phosphate (DHAPP) is an artemisinin based combined therapy and is very effective in treating malaria in areas of high resistance to conventional malaria. The present study investigates the toxicological effects of the use therapeutic dose of DHAPP in male and female rats. Thirty adult Wister rats of both sexes weighing between 180 and 210 g were grouped into three consisting of 5 males and 5 females per group. The control group was orally administered with normal saline, the test and recovery groups were given body weight 15.4 mg/kg of DHAPP orally for three days after which the recovery group were allowed to recover from the drug’s effect for another three days. The blood samples were collected through cardiac puncture into heparinised tubes centrifuged at 5000 rpm for 10 minutes. The kidney were also removed, weighed, blotted dry and homogenised. The supernatant of each of the plasma and kidney was kept in clean bottles, stored at -4oC and were used for kidney function and histological analysis.An increment was observed in the protein, creatinine and urea levels in the plasma while in the kidney, the levels decreased. In the plasma and kidney, all the biochemical parameters were observed to return to normal when the animals were left to recover. Sex related differences were noted in most of the groups in the plasma and kidney of the enzyme activities. Histological examination also revealed an intoxication of the kidney cell of the rats.It could therefore be inferred from these results that increases in protein, creatinine and urea levels in the blood plasma showed the possibility of abnormality in the renal system when the drug was administered. It is therefore recommended that the drug should be administered with caution.


Dihydroartemisinin-piperaquine phosphate (DHAPP), artemisinin, antimalarial, therapeutic dose

Full Text:



Whitty, C.J.M., Allan, R., Wiseman, V., Ochola, S., Nakyanzi-Mugisha, M.V., Vonhm, B., Mwita, M., Miaka, C., Oloo, A., Premji, Z., Burgess, C. and Mutabingwa, T.K. (2004). Averting a Malaria Disaster in Africa – Where Does the Buck Stop? Bulletin of the World Health Organization, 82, 381-384.

Greenwood, B.M., Bojang, K., Whitty, C.J. and Targett, G.A. (2005). Malaria. Lancet, 365, 1487-1498.

Olayinka, E.T. and Ore, A. (2013). Alterations in Antioxidant Status and Biochemical Indices Following Administration of Dihydroartemisinin-Piperaquine Phosphate (P-Alaxin). Journal of Pharmacy and Biological Sciences, 5, 43-53.

Sutherland, C. J., Tanomsing, N., Nolder, D., Oguike, M.,Jennison, C., Pukrittayakamee, S., Dolecek, D., Hein, T.T., do Rosario, V.E., Arez, A.P., Pinto, J., Michon, P., Escalante, A.A., Nosten, F., Burke, M., Lee, R., Blaze, M., Otto, T.D., Barnwell, J., Pain, A., Williams, J.E., White, N.J., Day, N.P., Snounou, G., Lockhart, P.L., Chiodini, P.L., Imwong, M. and Polley, S.D. (2010). Two Non-recombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally. Journal of Infectious Diseases, 201(10), 1544-1550.

World Health Organization. (2011).National Guidelines For diagnosis and Treatment of Malaria. World Health Organization, Geneva. Pp.1-52.

Christopher, J.L., Lisa C. R., Stephen S. L., Kathryn G.A., Kyle, J.M.N., Rafael, L. and Alan, D.L. (2012). Global Malaria Mortality between 1980 and 2012: A Systematic Analysis.

Fong, Y.L., Cadigan, F.C. and Coatney, G.R. (1971). A Presumptive Case of Naturally OccuringPlasmodium knowlesiMalaria in Man in Malaysia. Transactions of the Royal Society of Tropical Medicine and Hygiene, 65, 839-840.

Sibley, C.H., Hyde, J.E., Sims, P.F.G., Plowe, C.V., Kublin, J.G., Mberu, E.K., Cowman, A.F., Winstanley, P.A., Watkins, W.M. and Nzila, A.M. (2001). Pyrimethamine sulfadoxine Resistance in Plasmodium falciparum; What is Next. Trends in Parasitology, 17, 582-588.

Antinori, S., Galimberti, L., Milazzo, L. and Corbellino, M. (2012). Plasmodium knowlesi: The Emerging Zoonotic Malaria Parasite. Acta Tropica, 125, 191-201.

Singh, B., Sung, L.K., Matusop, A., Radhakrishnan, A., Shamsul, S.S. and Singh, J. (2004). A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet, 363, 1017–1024.

Spinello, A., Laura, G., Laura, M. and Mario, C. (2013). Plasmodium knowlesi: The emerging zoonotic malaria parasite. Acta Tropica, 125, 191– 201.

Adumanya, O.C., Uwakwe, A.A., Odeghe O.B., Essien, E.B. and Eneke, I.C. (2012).The Comparative Effects of Some Selected Supplements on the Antimalarial Activity of Camoquine and Artesunate. International Journal of Pure Applied Science Technology, 10, 51-57

Kilama, W. and Ntoumi, F. (2009). Malaria: a research agenda for the eradication era. Lancet, 374, 1480–1482.

Centre for Disease Control and Prevention. (2008). Malaria Rapid Growth Diagnostic Performance. Atlanta.

World Health Organization. (2005). Treatment of Malaria. World Health Organization, Geneva. Pp.1-4.

American Physiological Society (2002). Guiding principles for research involving animals and human beings. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 283, 281–283.

Gornall, A.G., Bardawil, C.J. and David, M.M. (1949). Determination of Serum Proteins by Means of the Biuret Reaction. Journal of Biological Chemistry, 177, 751-766.

Association of Official Analytical Chemists. (2000). Official methods analytical chemists. Arlington, Virginia, USA.

Drury, R.A.B., Wallington E.A. and Cameron R. (1967). Carleton’s histological technique, 4th histopathological technique and practical histochemistry, 4rd edition, Oxford University Press, New York, USA. Pp. 279- 280.

Obianime, A.W. and Aprioku, J.S. (2011). Mechanism of Action of Artemisinins on Biochemical Hematological and Reproductive Parameters in Male Guinea Pigs. International Journal of Pharmacology, 7, 84-93.

Offie, P., Sodin, I., Sarah, H, Chung, I., Donald, R. and Mattison, A. (2011). Sex Differences in Drug Disposition. Journal of Biomedicine and Biotechnology, Pp. 1-14. doi:10.1155/2011/187103

Ngokere, A.A., Ngokere, T.C. and Ikwudinma, A.P. (2004). Acute Study of Histomorphological and Biochemical Changes Caused by Artemisinin in Visceral Organs of the Rabbit. Journal of Experimental Clinical Analysis, 3, 11-16.


  • There are currently no refbacks.

Copyright © 2018 Journal of Progressive Research in Modern Physics and ChemistryAll rights reserved.

ISSN: 2456-6438

For any query/support contact us at,,