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Environ Toxicol. 2015 Mar;30(3):301-7. doi: 10.1002/tox.21907. Epub 2013 Sep 25.

Toxicity associated with repeated administration of artemether-lumefantrine in rats.

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  • 1Cancer 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.

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.

© 2013 Wiley Periodicals, Inc.

KEYWORDS:

anti-malaria; artemether-lumefantrine; drug misuse; drug toxicity; micronucleated polychromatic erythrocytes

PMID:
24115283
[PubMed - in process]
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