title: Toxicity associated with repeated administration of artemether-lumefantrine in rats.
abstract: Chemotherapy remains an important approach in the fight against malaria. Artemether-lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether-lumefantrine in rats. Graded doses of artemether-lumefantrine (1-5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether-lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether-lumefantrine treated rats were significantly higher (p < 0.05) than that of the negative control group indicating that repeated administration of artemether-lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross-section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced (p < 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused.
authors.affiliation: Cancer Research and Molecular Biology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Solomon E
authors.initials: SE
authors.lastname: Owumi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gbadegesin
authors.forename: Oyeronke A
authors.initials: OA
authors.lastname: Odunola
authors.forename: Ayodeji M
authors.initials: AM
authors.lastname: Adegoke
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Uwaifo
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects; D004983:Ethanolamines / Q000633:toxicity*; D005449:Fluorenes / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: anti-malaria; artemether-lumefantrine; drug misuse; drug toxicity; micronucleated polychromatic erythrocytes