title: Artesunate-amodiaquine combination therapy in the absence of malarial parasite infection induces oxidative damage in female rats.
abstract: Artesunate-amodiaquine is among the most widely available artemisinin combination therapy used as treatment regimen for uncomplicated Plasmodium falciparum malaria. Our aim was to evaluate clinical routine markers of liver and renal functions, lipid profile levels and lipid peroxidation status in a female mammalian rat model. This was an attempt to simulate a scenario where the drugs are taken without malarial parasite infection, which is a common practice in settings where drug misuse is a common practice. Twenty female Wistar rats were randomly divided into four study groups of five animals each. Group 1 (control) received distilled water, group 2 was exposed to artesunate [2 mg/kg body weight (b.w.)], group 3 was administered with amodiaquine (6.12 mg/kg b.w.) and group 4 was co-administered with artesunate (2 mg/kg b.w.) and amodiaquine (6.12 mg/kg b.w.) for 3 days. At the end of the treatment period, animals were fasted overnight and sacrificed. Markers of liver and renal functions and lipid profile indices were evaluated in the plasma, whereas lipid peroxidation status, GSH concentration and G6PD activity were assessed in the erythrocytes. The results showed that the co-administration of artesunate and amodiaquine altered liver function markers and lipid profile indices. The drugs also induced lipid peroxidation as evidenced by the elevated level of oxidative stress marker malondialdehyde (p < 0.05). We recommend therefore that the drugs should be taken with prescription only with clinical evidence of malarial parasite infection.
authors.affiliation: Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Amos O
authors.initials: AO
authors.lastname: Abolaji
authors.forename: Fenose
authors.initials: F
authors.lastname: Osedeme
authors.forename: Oluwatosin
authors.initials: O
authors.lastname: Olusemire
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016778:Malaria, Falciparum / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine
keywords: combination therapy; drug misuse; erythrocyte; malaria; oxidative stress