Guidet B R, Shah S V
Department of Medicine, Tulane Medical School, New Orleans, Louisiana.
Am J Physiol. 1989 Jan;256(1 Pt 2):F158-64. doi: 10.1152/ajprenal.1989.256.1.F158.
The purpose of this study was to demonstrate in vivo generation of hydrogen peroxide by rat renal cortex and glomeruli. Aminotriazole irreversibly inactivates catalase only in the presence of hydrogen peroxide, and previous studies have shown that aminotriazole-mediated inhibition of catalase is a measure of in vivo changes in the hydrogen peroxide generation. Aminotriazole injected intraperitoneally caused a dose-dependent (0.1-1 g/kg) and a time-dependent (15, 30, 60, 90, 120 min) inhibition of the catalase activity in renal cortex. We confirmed that catalase inactivation by aminotriazole was due to formation of a catalase-hydrogen peroxide intermediate (compound I) because catalase inactivation was prevented by ethanol (2 g/kg), a competitive substrate for compound I. The specific activity of catalase in the glomeruli [0.27 +/- 0.026 k/mg protein (where k is the first-order reaction rate constant), n = 5] was significantly lower than the specific activity in the tubules (1.04 +/- 0.15 k/mg protein, n = 5) obtained from the same rats. The residual catalase activity (RCA) in the glomeruli (0.05 +/- 0.01 k/mg protein) was 19% of control values at 90 min after aminotriazole injection (1 g/kg). Taken together these data provide evidence for in vivo generation of hydrogen peroxide by rat renal cortex and glomeruli under normal conditions. Aminotriazole-mediated inhibition of catalase has been used in previous studies as a measure of in vivo changes in the hydrogen peroxide generation.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是证明大鼠肾皮质和肾小球在体内产生过氧化氢。氨基三唑仅在过氧化氢存在时不可逆地使过氧化氢酶失活,并且先前的研究表明,氨基三唑介导的过氧化氢酶抑制是体内过氧化氢生成变化的一种度量。腹腔注射氨基三唑会导致肾皮质中过氧化氢酶活性呈剂量依赖性(0.1 - 1 g/kg)和时间依赖性(15、30、60、90、120分钟)的抑制。我们证实氨基三唑导致的过氧化氢酶失活是由于形成了过氧化氢酶 - 过氧化氢中间体(化合物I),因为乙醇(2 g/kg)可防止过氧化氢酶失活,乙醇是化合物I的竞争性底物。来自相同大鼠的肾小球中过氧化氢酶的比活性[0.27±0.026 k/毫克蛋白(其中k是一级反应速率常数),n = 5]显著低于肾小管中的比活性(1.04±0.15 k/毫克蛋白,n = 5)。在注射氨基三唑(1 g/kg)90分钟后,肾小球中的残余过氧化氢酶活性(RCA)为(0.05±0.01 k/毫克蛋白),是对照值的19%。这些数据共同提供了证据,证明在正常条件下大鼠肾皮质和肾小球在体内产生过氧化氢。在先前的研究中,氨基三唑介导的过氧化氢酶抑制已被用作体内过氧化氢生成变化的一种度量。(摘要截断于250字)