Antiplasmodial activity of desloratadine-dihydroartemisinin-piperaquine on Plasmodium berghei infected mice

Udeme Owunari Georgewill; Nwakaego Omonigho Ebong; Elias Adikwu

doi:10.7324/JABB.2021.9217

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Abstract

This study examined the antiplasmodial effect of desloratadine-dihydroartemisinin-piperaquine (DL/D/P) on Plasmodium berghei infected mice. Adult mice (22–25 g) were grouped, inoculated with P. berghei, and treated orally with DL (5 mg/kg), D/P (1.71/13.7 mg/kg), and DL/D/P daily for 4 days. The negative and positive controls were treated orally with normal saline (0.2 mL) and chloroquine (10 mg/kg), respectively, for 4 days. After treatment, blood samples were assessed for percentage parasitemia and serum biochemical parameters. Mice were also observed for mean survival time (MST). In the curative, suppressive, and prophylactic studies, DL, D/P, and DL/D/P significantly decreased percentage parasitemia levels at P < 0.01, P < 0.001, and P < 0.0001, respectively, when compared to negative control (NC). DL, D/P, and DL/D/P significantly increased MST at P < 0.05, P < 0.01, and P < 0.001, respectively, when compared to NC. Significant (P < 0.001) decreases in packed cell volume, red blood cells, hemoglobin, and high-density lipoprotein cholesterol levels with significant (P < 0.001) increases in total cholesterol, white blood cells, low-density lipoprotein cholesterol, and triglyceride levels were observed in NC when compared to normal control. However, the aforementioned parameters were restored by DL (P < 0.05), D/P (P < 0.01), and DL/D/P (P < 0.001) when compared to NC. DL/D/P may be an effective antimalarial drug combination.

Keyword: Desloratadine Dihydroartemisinin/piperaquine malaria Mice.

Citation:

Georgewill UO, Ebong NO, Adikwu E. Antiplasmodial activity of desloratadine-dihydroartemisinin-piperaquine on Plasmodium berghei infected mice. 2021;9(2):169-173.

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

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Reference

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2. Mueller I, Zimmerman PA, Reeder JC. Plasmodium malariae and Plasmodium ovale--the bashful malaria parasites. Trends Parasitol 2007;23:278-83. https://doi.org/10.1016/j.pt.2007.04.009
3. World Health Organisation. Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000-2010. Geneva: World Health Organisation; 2010.
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5. Nzila A, Ma Z, Chibale K. Drug repositioning in the treatment of malaria and TB. Future Med Chem 2011;3:1413-26. https://doi.org/10.4155/fmc.11.95
6. Walker SL, Waters MF, Lockwood DN. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev 2007;78:197-215. https://doi.org/10.47276/lr.78.3.197
7. Burrows JN, Leroy D, Lotharius J, Waterson D. Challenges in antimalarial drug discovery. Future Med Chem 2011;3:1401-12. https://doi.org/10.4155/fmc.11.91
8. Beghdadi W, Porcherie A, Schneider BS, Dubayle D, Peronet R, Huerre M, et al. Role of histamine and histamine receptors in the pathogenesis of malaria. Méd Sci 2019;25:377-81. https://doi.org/10.1051/medsci/2009254377
9. Sowunmi A, Oduola AM, Ogundahunsi OA, Falade CO, Gbotosho GO, Salako LA. Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicatedfalciparum malaria in children. Trans R Soc Trop Med Hyg 1997;91:63-7. https://doi.org/10.1016/S0035-9203(97)90399-0
10. Peters W, Ekong R, Robinson BL, Warhurst DC, Pan X. The chemotherapy of rodent malaria. XLV. Reversal of chloroquine resistance in rodent and human Plasmodium by antihistaminic agents. Ann Trop Med Parasitol 1990;84:541-51. https://doi.org/10.1080/00034983.1990.11812509
11. Anthes JC, Gilchrest H, Richard C, Eckel S, Hesk D, West RE, et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H(1) receptor. Eur J Pharmacol 2002;449:229-37. https://doi.org/10.1016/S0014-2999(02)02049-6
12. Yavo W, Faye B, Kuete T, Djohan V, Oga SA, Kassi RR, et al. Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa. Malar J 2011;10:198. https://doi.org/10.1186/1475-2875-10-198
13. Affrime M, Gupta S, Banfield C. Cohen A. A pharmacokinetic profile of desloratadine in healthy adults, including elderly. Clin Pharmacokinet 2002;41:13-9. https://doi.org/10.2165/00003088-200241001-00003
14. Somsak V, Damkaew A, Onrak P. Antimalarial activity of kaempferol and its combination with chloroquine in Plasmodium berghei infection in mice. J Path 2018;2018:1-7. https://doi.org/10.1155/2018/3912090
15. Ryley JF, Peters W. The antimalarial activity of some quinolone esters. Ann Trop Med Parasitol 1970;84:209-22. https://doi.org/10.1080/00034983.1970.11686683
16. Knight DJ, Peters W. The antimalarial action of N-benzyl oxydihydrotriazines and the studies on its mode of action. Ann Trop Med Par 1980;74:393-404. https://doi.org/10.1080/00034983.1980.11687360
17. Peters W. Rational methods in the search for antimalarial drugs. Trans R Soc Trop Med Hyg 1967;61:400-10. https://doi.org/10.1016/0035-9203(67)90015-6
18. WHO Guidelines for the Treatment of Malaria 2006. Available from: http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf. [Last accessed on 2020 Jul 21].
19. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, et al. The role of animal models for research on severe malaria. PLoS Pathog 2012;8:1-8. https://doi.org/10.1371/journal.ppat.1002401
20. Akanbi OM. In vivo study of anti-plasmodia activity of Terminalia avicennioides and its effect on lipid profile and oxidative stress in mice infected with Plasmodium berghei. Br Microbiol Res 2013;3:501-12. https://doi.org/10.9734/BMRJ/2013/3680
21. Haldar K, Mohandas N. Malaria, erythrocytic infection, and anemia. Hematology Am Soc Hematol Educ Program 2009. Doi: 10.1182/ asheducation-2009.1.87. https://doi.org/10.1182/asheducation-2009.1.87
22. Adekunle AS, Adekunle OC, Egbewale BE. Serum status of selected biochemical parameters in malaria: An animal model. Biol Res 2007;18:109-13.
23. Mohanty S, Mishra SK, Das BS, Satpathy SK, Mohanty D, Patnaik JK, et al. Altered plasma lipid pattern in falciparum malaria. Ann Trop Med Parasitol 1992;86:601-6. https://doi.org/10.1080/00034983.1992.11812715
24. Meshnick SR. The mode of action of antimalarial endoperoxides. Trans R Soc Trop Med Hyg 1994;88:131-2. https://doi.org/10.1016/0035-9203(94)90468-5
25. Tärning J. Piperaquine, Bioanalysis, Drug Metabolism and Pharmacokinetics. Göteborg, Sweden: Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at Göteborg University; 2007.

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1. World Health Organization. World Malaria Report 2019. Available from: https://www.who.int/publicationsdetail/world-malaria-report-2019. [Last accessed on 2020 Sep 13].

2. Mueller I, Zimmerman PA, Reeder JC. Plasmodium malariae and Plasmodium ovale--the bashful malaria parasites. Trends Parasitol 2007;23:278-83. https://doi.org/10.1016/j.pt.2007.04.009

3. World Health Organisation. Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000-2010. Geneva: World Health Organisation; 2010.

4. Aneesa S. Evaluation of Antihistamines for in Vitro Antimalarial Activity Against Plasmodium falciparum. 2011. Available from: https://www.api.semanticscholar.org/CorpusID:82705763. [Last accessed on 2020 Aug 14].

5. Nzila A, Ma Z, Chibale K. Drug repositioning in the treatment of malaria and TB. Future Med Chem 2011;3:1413-26. https://doi.org/10.4155/fmc.11.95

6. Walker SL, Waters MF, Lockwood DN. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev 2007;78:197-215. https://doi.org/10.47276/lr.78.3.197

7. Burrows JN, Leroy D, Lotharius J, Waterson D. Challenges in antimalarial drug discovery. Future Med Chem 2011;3:1401-12. https://doi.org/10.4155/fmc.11.91

8. Beghdadi W, Porcherie A, Schneider BS, Dubayle D, Peronet R, Huerre M, et al. Role of histamine and histamine receptors in the pathogenesis of malaria. Méd Sci 2019;25:377-81. https://doi.org/10.1051/medsci/2009254377

9. Sowunmi A, Oduola AM, Ogundahunsi OA, Falade CO, Gbotosho GO, Salako LA. Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicatedfalciparum malaria in children. Trans R Soc Trop Med Hyg 1997;91:63-7. https://doi.org/10.1016/S0035-9203(97)90399-0

10. Peters W, Ekong R, Robinson BL, Warhurst DC, Pan X. The chemotherapy of rodent malaria. XLV. Reversal of chloroquine resistance in rodent and human Plasmodium by antihistaminic agents. Ann Trop Med Parasitol 1990;84:541-51. https://doi.org/10.1080/00034983.1990.11812509

11. Anthes JC, Gilchrest H, Richard C, Eckel S, Hesk D, West RE, et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H(1) receptor. Eur J Pharmacol 2002;449:229-37. https://doi.org/10.1016/S0014-2999(02)02049-6

12. Yavo W, Faye B, Kuete T, Djohan V, Oga SA, Kassi RR, et al. Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa. Malar J 2011;10:198. https://doi.org/10.1186/1475-2875-10-198

13. Affrime M, Gupta S, Banfield C. Cohen A. A pharmacokinetic profile of desloratadine in healthy adults, including elderly. Clin Pharmacokinet 2002;41:13-9. https://doi.org/10.2165/00003088-200241001-00003

14. Somsak V, Damkaew A, Onrak P. Antimalarial activity of kaempferol and its combination with chloroquine in Plasmodium berghei infection in mice. J Path 2018;2018:1-7. https://doi.org/10.1155/2018/3912090

15. Ryley JF, Peters W. The antimalarial activity of some quinolone esters. Ann Trop Med Parasitol 1970;84:209-22. https://doi.org/10.1080/00034983.1970.11686683

16. Knight DJ, Peters W. The antimalarial action of N-benzyl oxydihydrotriazines and the studies on its mode of action. Ann Trop Med Par 1980;74:393-404. https://doi.org/10.1080/00034983.1980.11687360

17. Peters W. Rational methods in the search for antimalarial drugs. Trans R Soc Trop Med Hyg 1967;61:400-10. https://doi.org/10.1016/0035-9203(67)90015-6

18. WHO Guidelines for the Treatment of Malaria 2006. Available from: http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf. [Last accessed on 2020 Jul 21].

19. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, et al. The role of animal models for research on severe malaria. PLoS Pathog 2012;8:1-8. https://doi.org/10.1371/journal.ppat.1002401

20. Akanbi OM. In vivo study of anti-plasmodia activity of Terminalia avicennioides and its effect on lipid profile and oxidative stress in mice infected with Plasmodium berghei. Br Microbiol Res 2013;3:501-12. https://doi.org/10.9734/BMRJ/2013/3680

21. Haldar K, Mohandas N. Malaria, erythrocytic infection, and anemia. Hematology Am Soc Hematol Educ Program 2009. Doi: 10.1182/ asheducation-2009.1.87. https://doi.org/10.1182/asheducation-2009.1.87

22. Adekunle AS, Adekunle OC, Egbewale BE. Serum status of selected biochemical parameters in malaria: An animal model. Biol Res 2007;18:109-13.

23. Mohanty S, Mishra SK, Das BS, Satpathy SK, Mohanty D, Patnaik JK, et al. Altered plasma lipid pattern in falciparum malaria. Ann Trop Med Parasitol 1992;86:601-6. https://doi.org/10.1080/00034983.1992.11812715

24. Meshnick SR. The mode of action of antimalarial endoperoxides. Trans R Soc Trop Med Hyg 1994;88:131-2. https://doi.org/10.1016/0035-9203(94)90468-5

25. Tärning J. Piperaquine, Bioanalysis, Drug Metabolism and Pharmacokinetics. Göteborg, Sweden: Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at Göteborg University; 2007.