Zenser T V, Mattammal M B, Rapp N S, Davis B B
J Lab Clin Med. 1983 Jan;101(1):58-65.
The effect of in vivo and in vitro aspirin treatment on renal inner medullary prostaglandin hydroperoxidase-catalyzed metabolism of acetaminophen and benzidine was examined. Metabolism was assessed by the binding of [3H]acetaminophen and [14C]benzidine to TCA-precipitable material. Microsomes were prepared from control or aspirin-treated rabbits. Aspirin, whether administered in vivo (15 mg/kg i.v.) or added in vitro (2 mM), had no effect on peroxide-initiated metabolism. By contrast, arachidonic acid-initiated metabolism was completely prevented by both in vivo and in vitro aspirin. Salicylate did not inhibit either arachidonic acid- or peroxide-dependent metabolism. The antioxidant glutathione (1 mM) completely inhibited both peroxide- and arachidonic acid-initiated metabolism. Aspirin treatment completely inhibited metabolism of arachidonic acid by medullary microsomes. Thus aspirin does not inhibit the hydroperoxidase component of prostaglandin endoperoxide synthetase, and co-oxidation of acetaminophen and benzidine may proceed in the presence of aspirin. Co-oxidation may be involved in the genesis of the nephrotoxicity of mixed analgesic abuse.
研究了体内和体外阿司匹林处理对肾内髓质前列腺素氢过氧化物酶催化对乙酰氨基酚和联苯胺代谢的影响。通过[3H]对乙酰氨基酚和[14C]联苯胺与三氯乙酸沉淀物质的结合来评估代谢。从对照或阿司匹林处理的兔子制备微粒体。阿司匹林，无论是体内给药（15mg/kg静脉注射）还是体外添加（2mM），对过氧化物引发的代谢均无影响。相比之下，体内和体外阿司匹林均完全抑制花生四烯酸引发的代谢。水杨酸盐不抑制花生四烯酸或过氧化物依赖性代谢。抗氧化剂谷胱甘肽（1mM）完全抑制过氧化物和花生四烯酸引发的代谢。阿司匹林处理完全抑制髓质微粒体对花生四烯酸的代谢。因此，阿司匹林不抑制前列腺素内过氧化物合酶的氢过氧化物酶成分，对乙酰氨基酚和联苯胺的共氧化可能在阿司匹林存在下进行。共氧化可能参与混合镇痛剂滥用肾毒性的发生。
