Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether-lumefantrine and halofantrine in rats.
Artemether, artemether-lumefantrine, or coartem and halofantrine are alternative antimalarial drugs to chloroquine. Their efficacy and potential to delay drug resistance in falciparum malaria had led to their increased use. Although these drugs have proven to be well tolerated, there are adverse effects associated with them. This study was designed to examine the toxic potential of acute administration of these drugs in rats. Twenty-four rats were divided into four groups: group I (control) received distilled water; group II received artemether for 5 days with an initial dose of 3.2 g/kg body weight on day 1 and 1.6 mg/kg body weight on days 2-5; group III received coartem (27 mg/kg body weight/day) for 3 days, which was divided into two equal portions per day; and group IV received halofantrine (24 mg/kg body weight/day) in three equal portions. Administration of artemether, coartem and halofantrine caused significant decrease (P < 0.05) in reduced glutathione levels in the liver by 29%, 21% and 26%, respectively. In contrast, there were no significant differences (P > 0.05) in the kidney glutathione levels. Furthermore, artemether, coartem and halofantrine decreased the liver- and kidney-enzymatic antioxidant status of the animals. Precisely, artemether, coartem and halofantrine decreased liver superoxide dismutase and catalase activities by 45%, 50% and 57%; and 20%, 29% and 23%, respectively. While the kidney catalase activities were decreased by 41%, 28% and 30%, respectively, the drugs however did not produce significant effect (P > 0.05) on the kidney superoxide dismutase activities. In addition, artemether, coartem and halofantrine decreased the hepatic levels of glutathione S-transferase by 64%, 51% and 53%, respectively. Administration of artemether, coartem and halofantrine significantly increased (P < 0.05) liver and kidney lipid peroxidation levels by 67%, 50% and 81%; and 58%, 43% and 31%, respectively. This indicates that the liver is considerably more affected than the kidneys. Similarly, halofantrine treatment caused significant elevation (P < 0.05) in the levels of serum creatinine, aspartate and alanine aminotransferases and blood urea nitrogen by 73%, 66%, 61% and 63%, respectively. These data indicate that oral administration of artemether, coartem and halofantrine has adverse effects on both enzymic and non-enzymatic antioxidant status of the animals.
Adaramoye
Oluwatosin A
OA
Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Osaimoje
Dorcas O
DO
Akinsanya
Adewale M
AM
Nneji
Chiaka M
CM
Fafunso
Michael A
MA
Ademowo
Olusegun G
OG
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism*; D000077549:Artemether; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000633:toxicity; D005449:Fluorenes / Q000008:administration & dosage* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000962:Antimalarials; D000975:Antioxidants; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D015415:Biomarkers; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D010616:Phenanthrenes; D003404:Creatinine; D000077549:Artemether; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C023768:halofantrine; D001663:Bilirubin