Cai Y, Sohlenius A K, Andersson K, Sundberg C, DePierre J W
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Biochem Pharmacol. 1994 Jun 15;47(12):2213-9. doi: 10.1016/0006-2952(94)90258-5.
Male C57 BL/6 mice were exposed to 1.0% (w/w) acetylsalicylic acid (ASA) in their diet for 10 days and effects related to peroxisome proliferation were subsequently examined. A 2.2-fold increase in mitochondrial protein content was obtained. The activities of the peroxisomal enzymes, lauroyl-CoA oxidase, palmitoyl-CoA oxidation and catalase, were enhanced 4.5-, 4.0- and 2.1-fold, respectively. There was a dramatic increase (9.1-fold) in microsomal cytochrome P450 IVA-catalysed activity, a 1.6-fold induction of total microsomal P450 content and a 2-fold induction of microsomal cytochrome P450 reductase activity (measured as NADPH-cytochrome c reductase). Catalase activity in the cytosol was induced 5.2-fold and DT-diaphorase activity was increased 3.5- and 3.2-fold in the cytosol and mitochondria, respectively. There was a significant increase in the susceptibility of microsomes to lipid peroxidation. Smaller increases in superoxide dismutase, glutathione transferase and glutathione peroxidase activities were also observed. The possible relevance of these effects to the pharmacology of ASA is discussed.
将雄性C57 BL/6小鼠的饮食中添加1.0%（w/w）的乙酰水杨酸（ASA），持续10天，随后检测与过氧化物酶体增殖相关的影响。线粒体蛋白含量增加了2.2倍。过氧化物酶体酶月桂酰辅酶A氧化酶、棕榈酰辅酶A氧化酶和过氧化氢酶的活性分别增强了4.5倍、4.0倍和2.1倍。微粒体细胞色素P450 IVA催化活性显著增加（9.1倍），微粒体总细胞色素P450含量诱导增加1.6倍，微粒体细胞色素P450还原酶活性诱导增加2倍（以NADPH-细胞色素c还原酶测量）。胞质中的过氧化氢酶活性诱导增加5.2倍，胞质和线粒体中的DT-黄递酶活性分别增加3.5倍和3.2倍。微粒体对脂质过氧化的敏感性显著增加。超氧化物歧化酶、谷胱甘肽转移酶和谷胱甘肽过氧化物酶活性也有较小程度的增加。讨论了这些影响与ASA药理学的可能相关性。
