Subacute Therapeutic Dosing of Artemether-Lumefantrine and Artesunate-Amodiaquine Combination Preserves Plasma Cholesterol, Renal Antioxidant Status, and Organ Weights in Rats
Recent instances of breakdowns of malaria control programs and the constant emergence of drug-resistant parasites to monotherapies have shored up the use of artemisinin-based combination therapy (ACT) as the malaria therapy of choice. We evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats. Sixteen albino rats were grouped into three. Group A ( ？？ = 5 ) served as the control. Groups B ( ？？ = 6 ) and C ( ？？ = 5 ) were administered, twice daily, oral therapeutic doses of artemether-lumefantrine (1.14/6.86？mg/kg/d) and artesunate-amodiaquine (2.86/8.58？mg/kg/d), respectively, for seven days. From our results, ACTs did not significantly ( ？？ > 0 . 0 5 ) alter catalase, superoxide dismutase, glutathione S-transferase, myeloperoxidase, and total glutathione levels when compared with the control. Plasma total cholesterol levels also decreased insignificantly ( ？？ > 0 . 0 5 ). Organ-system weights were not significantly ( ？？ > 0 . 0 5 ) different from control rats. Artesunate-amodiaquine, but not artemether-lumefantrine, significantly increased ( ？？ < 0 . 0 5 ) lactate dehydrogenase activity and also afforded a 27.2% decrease in heart weight when compared with control. Also, both ACTs increased ( ？？ < 0 . 0 5 ) lipid peroxidation. Overall, artesunate-amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ weights in vivo. However, caution is required above therapeutic indications or in chronic doses as this may predispose to renal oxidative stress. 1. Introduction Malarial infection is an important tropical mosquito-borne infectious disease that kills approximately three million per year. Statistics show that close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden [1, 2]. Over the years, different categories of plasmodia specie (Plasmodium falciparum, ovale, vivax, and malaria) evolved with several newly observed mechanisms of resistance. The emergence and spread across sub-Saharan Africa of Plasmodium falciparum resistance among others to the inexpensive antimalarials chloroquine and sulfadoxine-pyrimethamine have worsened the pandemic and hampered the socioeconomic development of affected countries [3]. Following increased resistance of malaria parasites to conventional drugs in the malarial regions of the world, the WHO has been promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria
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