Effect of three structurally related antimalarial drugs on liver microsomal components and lipid peroxidation in rats

Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology Pub Date : 2000-07-01 DOI:10.1016/S0742-8413(00)00116-X

E.Olatunde Farombi, Babatunde I Olowu, Godwin O Emerole

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引用次数: 56

Abstract

Changes in microsomal drug oxidizing enzymes, microsomal lipids, hepatic glutathione (GSH), glutathione S-transferase (GST) and malondialdehyde (MDA) formation following administration of rats with therapeutic doses of three structurally related antimalarial drugs, amodiaquine (AQ), mefloquine (MQ) and halofantrine (HF) were investigated. There was a significant decrease in the activities of aniline hydroxylase, p-nitroanisole O-demethylase and pentoxyresorufin O-dealkylase in AQ, MQ and HF treated rats. AQ elicited the greatest effect with 50, 37 and 67% reductions in the activities of aniline hydroxylase, p-nitroanisole O-demethylase and pentoxyresorufin O-dealkylase, respectively. All the drugs prolonged hexobarbital-sleeping time to varying extents. The three drugs increased significantly the cholesterol per phospholipid ratio. AQ, MQ and HF decreased significantly the GSH level, GST activity and increased the formation of MDA. The results indicate that the alterations in hepatic microsomal components and lipid peroxidation caused by the antimalarials are related to the structural differences in the compounds.

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三种结构相关抗疟药对大鼠肝微粒体成分和脂质过氧化的影响

研究了大鼠给药后微粒体药物氧化酶、微粒体脂质、肝谷胱甘肽(GSH)、谷胱甘肽s -转移酶(GST)和丙二醛(MDA)形成的变化。AQ、MQ和HF处理大鼠的苯胺羟化酶、对硝基苯甲醚o -去甲基化酶和戊氧基间苯二酚o -脱烷基酶活性均显著降低。AQ对苯胺羟化酶、对硝基苯甲醚o -去甲基化酶和戊氧基间苯二酚o -脱烷基酶活性分别降低50%、37%和67%，影响最大。所有药物都不同程度地延长了六巴比妥睡眠时间。三种药物均显著提高胆固醇/磷脂比值。AQ、MQ和HF显著降低GSH水平、GST活性，增加MDA的形成。结果表明，抗疟药引起的肝微粒体成分和脂质过氧化的改变与化合物的结构差异有关。

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Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology

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