BIOCHEMICAL AND HISTOPATHOLOGICAL EFFECTS OF COADMINISTRATION OF AMODIAQUINE, ARTESUNATE, AND SELENIUM ON PLASMODIUM BERGHEI INFECTED MICE
Objective: The effect of coadministering artesunate (ART), amodiaquine (AMO), and selenium were studied on mice induced with Plasmodium berghei.
Methods: The study was conducted using 6 groups of 6 male mice each. Group A constitutes the negative control (unparasitized) while Group B represents the parasite control (parasitized) group. Mice in Groups C, D, E and F, respectively, received 2 mg/kg bw of ART, 6.12 mg/kg bw of AMO, combination of AMO and ART, and 0.945 mg/kg bw of selenium in addition to ART and AMO for 3 days. Thereafter, animals were anesthetized, and the organs were excised. Liver homogenate was prepared and used for analysis of for aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total protein (TP), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde).
Results: The results showed no significant alteration in AST and ALT, but ALP was significantly (p<0.05) increased in Group D. In addition, a significant drop (p<0.05) in GSH and SOD activities and significant (p<0.05) increase in TP was observed in group E. Histopathological studies revealed no degenerative change in the morphology of the hepatocytes of mice in Group F whereas Groups D and E showed mild inflammatory cells.
Conclusion: Conclusively, the combination of ART-AMO therapy with selenium increases the efficacy and reduces potential toxicity of combined antimalarial drugs.
2. World Health Organization (WHO). World Malaria Report. Geneva, Switzerland: World Health Organization Press; 2017.
3. World Health Organization (WHO). World Malaria Report. Geneva, Switzerland: World Health Organization Press; 2016.
4. Perkins SL, Schall JA. Molecular phylogeny of malarial parasites recovered from cytochrome B gene sequences. J Parasitol 2002;88:972-8.
5. Ittarat W, Sreepian A, Srisarin A, Pathepchotivong K. Effect of dihydroartemisinin on the antioxidant capacity of P. falciparum-infected erythrocytes. Southeast. Asian J Trop Med Public Health 2003;34:744-50.
6. Nosten F, White NJ. Artemisinin-based combination treatment of falciparum Malaria. Am J Trop Med Hyg 2007;77:181-92.
7. Olliaro PL, Taylor WR. Developing artemisinin-based drug combinations for the treatment of drug-resistant falciparum Malariaâ€™. A review. J Postgrad Med 2004;50:40-4.
8. Brasseur P, Agnamey P, Gaye O, Vaillant M, Taylor WR, Olliaro PL. Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, Southern Senegal. Malar J 2007;6:150.
9. Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, et al. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum Malaria in Zanzibar, Tanzania. Clin Infect Dis 2005;41:1079-86.
10. Durrani N, Leslie T, Rahim S, Graham K, Ahmad F, Rowland M. Efficacy of combination therapy with artesunate plus amodiaquine compared to monotherapy with chloroquine, amodiaquine or sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum in Afghanistan. Trop Med Int Health 2005;10:521-9.
11. Newland LW. Handbook of Environmental Chemistry. New York: Springer-Verlag; 1982.
12. Stadtman TC. Some selenium-dependent biochemical processes. Adv Enzymol Relat Areas Mol Biol 1979;48:1-28.
13. Brown KM, Arthur JR. Selenium, selenoproteins and human health: A review. Public Health Nutr 2001;4:593-9.
14. Reitman S, Frankel SA. Colorimetric method for the determination of serum oxaloacetic and glutamic pyruvate transaminase. Am J Clin Pathol 1957;28:56-63.
15. Wright PJ, Leathwood PD, Plummer DT. Enzymes in rat urine: Alkaline phosphatase. Enzymologia 1972;42:317-27.
16. Gonall AG, Bardawill CJ, David MM. Determination of total protein. J Biol Chem 1949;177:751-60.
17. Sedlak J, Lindsay RH. Estimation of total protein-bound, and nonprotein sulfhydryl groups in tissue with Elmanâ€™s reagent. Ann Biochem J 1968;25:1192-5.
18. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.
19. Sun M, Zigma S. An improved spectrophotometric assay of superoxide dismutase based on epinephrine antioxidation. Ann Biochem J 1978;90:81-9.
20. Aksenes A, Njaa L. Determination of catalase activity in fish. Comp Biochem Physiol 1981;69:893-6.
21. Aliyu R, Okoye ZS, Shier WT. The hepatoprotective cytochrome P450 enzyme inhibitor isolated from Nigerian medicinal plant Cochlospermum planchonii is a Zinc Salt. J Ethnopharmacol 1995;48:89-97.
22. Bhattacharyya D, Mukherjee R, Pandit S, Das N, Sur TK. Prevention of carbon tetrachloride induced hepatotoxicity in ratsâ€™ by hmmoliv (a poly herbal formulation). Indian J Pharmacol 2003;35:183-5.
23. Iyawe HO, Onigbinde AO. Chloroquine and vitamins combination effects on Plasmodium berghei induced oxidative stress. Int J Biochem Res 2012;2:120-5.
24. Erisir M, Beytut E, Aksakal M, Seyran A. Effect of vitamin E and/or selenium on alkaline phosphatase activity in the liver, kidneys and heart of prednisoloneâ€“injected rats. Kafkas Univ Vet Fak Derg 2010;16:21-5.
25. Klein CJ, Moser-Veillon PB, Schweitzer A, Douglass LW, Reynolds HN, Patterson KY, et al. Magnesium, calcium, zinc, and nitrogen loss in trauma patients during continuous renal replacement therapy. J Parenter Enteral Nutr 2002;26:77-92.
26. Abolaji AO, Eteng MU, Omonua O, Adenrele Y. Influence of co-administration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar Rats. Hum Exp Toxicol 2013;32:206-15.
27. Farombi EO, Syntum YY, Emerole GO. Influence of chloroquine treatment and P. falciparum malaria infection on some enzymatic and non-enzymatic antioxidant defines indices in humans. Drug Chem Toxicol 2003;26:59-71.
28. Adebayo AH, Olasehinde GI, Egbeola OA, Yakubu OF, Adeyemi AO, Adekeye BT. Enhanced Antioxidant Capacity Following Selenium Supplemented Antimalarial Therapy in Plasmodium berghei Infected Mice. AIP Conference Proceedings; 1954. 030019 2018.
29. PabÃ³n A, Carmona J, Burgos LC, Blair S. Oxidative stress in patients with non-complicated malaria. Clin Biochem 2003;36: 71-78.
30. Obianime AW, Aprioku JS. Comparative study of artesunate, ACTs and their combinants on the biochemical parameters of male Guinea pigs. Afr J Biotechnol 2009;8:5059-65.
31. Bhattacharya B, Chatterjee TK, Ghosh JK. Effects of chloroquine on lysosomal enzymes, NADPH-induced lipid peroxidation and antioxidant enzymes of rat retina. Biochem Pharmacol 1983; 32:2965 68.
32. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527-5.
33. Adelekan DA, Adeodu OO, Thurnham A. Comparative effect of malaria and malnutrition on plasma antioxidant vitamins in children. Ann Trop Pediatr 1997;17:223-27.
34. Carrillo M, Kanai S, Nokubo M, Ivy GO, Sato Y, Kitani K. (âˆ’) deprenylincreases activites of superoxide dismutase and catalase in stritum but not in hippocampus: The sex and age related differences in the optimal dose in the rats. Exp Neurol 1992;166:286-95.
35. Koracevic D, Koracenc GD, Djevic V. Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 2001;54:356-61.