Debnam P, Glanville S, Clark A G
School of Biological Science, Victoria University of Wellington, New Zealand.
Biochem Pharmacol. 1993 Mar 24;45(6):1227-33. doi: 10.1016/0006-2952(93)90274-z.
(1) Basic triphenylmethane dyes related to pararosanilin inhibit class alpha glutathione S-transferases (GSTs) from rat liver. The inhibitory potency of each dye correlates with its octanol-water partition coefficient. Values of Ki determined at pH 6.5 ranged from about 1 x 10(-7) M for Ethyl violet to 7 x 10(-5) M for Methyl green. GST 3-3, a class mu isoenzyme, was an order of magnitude less sensitive to inhibition by Ethyl violet. (2) All of the dyes tested were bleached to varying degrees by glutathione. The bleaching appears to result from the formation of an adduct between the dye and glutathione. At pH 6.5, adduct formation is significant only for Malachite green and Methyl green. There is kinetic evidence that for these dyes the adduct contributes significantly to the overall inhibition. It is probable that at physiological pH, all of the dyes would exist to a significant extent in the adduct form. (3) The dyes are excreted extensively in the bile, at least partly as the glutathione adduct. The free dye is regenerated on standing, it is assumed as a result of removal of glutathione by oxidation.
(1) 与副蔷薇苯胺相关的碱性三苯甲烷染料可抑制大鼠肝脏中的α类谷胱甘肽S-转移酶（GSTs）。每种染料的抑制效力与其正辛醇-水分配系数相关。在pH 6.5条件下测定的Ki值范围从乙基紫的约1×10⁻⁷ M到甲基绿的7×10⁻⁵ M。GST 3-3，一种μ类同工酶，对乙基紫抑制的敏感性低一个数量级。(2) 所有测试的染料都被谷胱甘肽不同程度地漂白。漂白似乎是由于染料与谷胱甘肽之间形成加合物所致。在pH 6.5时，加合物的形成仅对孔雀绿和甲基绿显著。有动力学证据表明，对于这些染料，加合物对总体抑制有显著贡献。在生理pH条件下，所有染料很可能在很大程度上以加合物形式存在。(3) 这些染料大量经胆汁排泄，至少部分以谷胱甘肽加合物的形式。静置时游离染料会再生，推测这是氧化去除谷胱甘肽的结果。
