Kumar Ajit, Tyagi Yogesh K, Ponnan Prija, Rohil Vishwajeet, Prasad Ashok K, Dwarkanath Bilekere S, Parmar Virinder S, Raj Hanumantharao G
Department of Biochemistry, V. P. Chest Institute, University of Delhi, Delhi-110007, India.
J Pharm Pharmacol. 2007 Jan;59(1):81-6. doi: 10.1211/jpp.59.1.0011.
Earlier observations carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins and quercetin pentaacetate in preventing the genotoxicity of aflatoxin B1 (AFB1). We have extended the observation to an acetoxy biscoumarin i.e. ellagic acid peracetate (EAPA), which unlike ellagic acid (EA) has demonstrated time-dependent inhibition of liver microsomes catalysed AFB1-epoxidation as measured by AFB1 binding to DNA. EAPA was more potent than EA in preventing bone marrow and lung cells from AFB1-induced genotoxicity. EAPA was acted upon by microsomal acetoxy drug:protein transacetylase (TAase) leading to modulation of the catalytic activity of certain functional proteins (cytochrome P450, NADPH cytochrome c reductase and glutathione S-transferase), possibly by way of protein acetylation.
我们实验室早期的观察突出了乙酰氧基4-甲基香豆素和槲皮素五乙酸酯预防黄曲霉毒素B1（AFB1）遗传毒性的作用方式。我们将观察范围扩展到一种乙酰氧基双香豆素，即全乙酰化鞣花酸（EAPA），与鞣花酸（EA）不同，EAPA已证明对肝微粒体催化的AFB1环氧化具有时间依赖性抑制作用，这通过AFB1与DNA的结合来衡量。在预防骨髓和肺细胞免受AFB1诱导的遗传毒性方面，EAPA比EA更有效。微粒体乙酰氧基药物：蛋白质转乙酰酶（TAase）作用于EAPA，可能通过蛋白质乙酰化的方式，导致某些功能蛋白（细胞色素P450、NADPH细胞色素c还原酶和谷胱甘肽S-转移酶）的催化活性发生调节。
