Wendel A, Fausel M, Safayhi H, Tiegs G, Otter R
Biochem Pharmacol. 1984 Oct 15;33(20):3241-5. doi: 10.1016/0006-2952(84)90084-4.
The anti-inflammatory compound 2-phenyl-1,2-benzoisoselenazol-3(2H)-on (PZ 51) catalysed GSSG formation from GSH in the presence of hydroperoxides in an NADPH/GSSG reductase system with the following rates (delta log GSH/min per molar selenium): 1.1 X 10(6) with H2O2, 1.2 X 10(6) with butylhydroperoxide, 1.7 X 10(6) with cumenehydroperoxide. The reaction catalysed by the sulphur analogue of PZ 51 was negligible. Similar results were obtained in a direct assay of GSH-Px activity based on GSH estimation by dithionitrobenzoate. The activation energy of the reaction was determined as 55 kJ/mol . deg in the presence of 30 mumol/1 PZ 51 compared to 36.5 kJ/mol . deg obtained in the presence of 1 nmol/1 pure GSH-Px isolated from bovine red blood cells. In mouse liver microsomes, NADPH-dependent aminopyrine dealkylation was totally inhibited in the presence of 50 mumol/1 PZ 51. In vivo experiments with Se-deficient mice showed that the Se-moiety of PZ 51 is not available for the synthesis of the selenoenzyme GSH-Px after dietary treatment or i.p. doses up to 25 mg Se as PZ 51 per kg body wt. After oral administration of labelled PZ 51, unlike with selenite, no radioactivity was incorporated into GSH-Px within 48 hr. The data suggest that several similarities between PZ 51 and the active site of GSH-Px exist, resulting in the capability of the compound to catalyse the GSH-Px reaction. An extracellular pharmacodynamic action of the drug seems likely.
抗炎化合物2-苯基-1,2-苯并异硒唑-3(2H)-酮（PZ 51）在NADPH/谷胱甘肽二硫化物还原酶系统中，于过氧化物存在的情况下，催化谷胱甘肽（GSH）生成谷胱甘肽二硫化物（GSSG），其反应速率如下（每摩尔硒每分钟的Δlog GSH）：与过氧化氢反应时为1.1×10⁶，与叔丁基过氧化氢反应时为1.2×10⁶，与异丙苯过氧化氢反应时为1.7×10⁶。PZ 51的硫类似物催化的反应可忽略不计。基于二硫代硝基苯甲酸对GSH的测定，在直接检测谷胱甘肽过氧化物酶（GSH-Px）活性时也得到了类似结果。该反应的活化能在存在30 μmol/L PZ 51时测定为55 kJ/mol·℃，而在存在从牛红细胞中分离出的1 nmol/L纯GSH-Px时为36.5 kJ/mol·℃。在小鼠肝微粒体中，存在50 μmol/L PZ 51时，NADPH依赖性氨基比林脱烷基反应被完全抑制。对缺硒小鼠进行的体内实验表明，经饮食处理或腹腔注射高达每千克体重25 mg作为PZ 51的硒后，PZ 51中的硒部分无法用于合成硒酶GSH-Px。口服标记的PZ 51后，与亚硒酸盐不同，48小时内没有放射性被整合到GSH-Px中。数据表明PZ 51与GSH-Px的活性位点之间存在若干相似之处，导致该化合物能够催化GSH-Px反应。该药物似乎可能具有细胞外药效学作用。
