Antimalarial drugs exacerbate rat liver microsomal lipid peroxidation in the presence of oxidants.
The study was undertaken to evaluate the effect of prior treatment of rats with the antimalarial drugs amodiaquine (AQ) mefloquine (MQ) and halofantrine (HF) on rat liver microsomal lipid peroxidation in the presence of 1 mM FeSO4, 1 mM ascorbate and 0.2 mM H2O2 (oxidants). Ingestion of alpha-tocopherol, a radical chain-breaking antioxidant was also included to assess the role of antioxidants in the drug treatment. In the presence of oxidants AQ, MQ and HF elicited 288%, 175% and 225% increases in malondialdehyde (MDA) formation while the drugs induced 125%, 63% and 31% increases in the absence of oxidants respectively. Similarly, AQ, MQ and HF induced lipid hydroperoxide formation by 380%, 256%, 360% respectively in the presence of oxidants and 172%, 136% and 92% in the absence of exogenously added oxidants respectively. a-tocopherol reduced AQ, MQ and HF-induced MDA formation by 40%, 55% and 52% respectively and lipid hydroperoxide formation by 53%, 59% and 54% respectively. Similarly, alpha-tocopherol attenuated the AQ, MQ and HF-induced MDA formation by 49%, 51% and 51% in the presence of oxidants and lipid hydroperoxide formation by 61%, 62% and 47% respectively. The results indicate that rat liver microsomal lipid peroxidation could be enhanced by antimalarial drugs in the presence of reactive oxygen species and this effect could be ameliorated by treatment with antioxidants.
Farombi
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Drug Metabolism and Toxicology Unit, Department of Biochemistry, University of Ibadan, Nigeria. ofarombi@ibadan.skannet.com
Adoro
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Uhunmwangho
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D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015767:Mefloquine / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010616:Phenanthrenes / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D024502:alpha-Tocopherol / Q000494:pharmacology
D000962:Antimalarials; D000975:Antioxidants; D005296:Ferrous Compounds; D008054:Lipid Peroxides; D016877:Oxidants; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D000655:Amodiaquine; C020748:ferrous sulfate; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; C023768:halofantrine; D015767:Mefloquine