title: Influence of coadministration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar rats.
abstract: Among the artemisinin-based combination therapy (ACT) regimens, artemisinin derivative, artemether in combination with lumefantrine (artemether-lumefantrine, AL) has achieved excellent results in the fight against malarial scourge. In this study, we evaluated the toxic potential of these drugs at the therapeutic doses in female Wistar rats. Animals were randomly divided into four groups: those administered 1% Tween 80 (control), those administered artemether (4 mg/kg body weight), those administered lumefantrine (24 mg/kg body weight), and those coadministered artemether (4 mg/kg body weight) and lumefantrine (24 mg/kg body weight). The drugs were orally administered twice daily for 3 days by gastric intubation after which selected plasma biochemical indices, and erythrocytes antioxidant defence and lipid peroxidation markers were evaluated. Coadministration of artemether and lumefantrine raised liver and renal function markers and increased atherogenic index. While reduced glutathione, glucose-6-phosphate dehydrogenase (G6PD) and catalase activities were reduced, glutathione peroxidase and glutathione-s-transferase activities increased in all the treated groups compared to the control group. The drugs caused significant (p < 0.05) elevation of malondialdehyde (MDA) levels compared to the control group. These results imply that coadministration of artemether and lumefantrine may increase the risks of atherosclerosis as well as liver and renal function impairments in the users. In addition, the drugs may also promote oxidative stress in the erythrocytes.
authors.affiliation: Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: A O
authors.initials: AO
authors.lastname: Abolaji
authors.forename: M U
authors.initials: MU
authors.lastname: Eteng
authors.forename: O
authors.initials: O
authors.lastname: Omonua
authors.forename: Y
authors.initials: Y
authors.lastname: Adenrele
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D002374:Catalase / Q000378:metabolism; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D000078102:Lumefantrine; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D008315:Malondialdehyde; C031327:artemisinin; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000078102:Lumefantrine; D005978:Glutathione