de Cavanagh E M, Fraga C G, Ferder L, Inserra F
Department of Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Am J Physiol. 1997 Feb;272(2 Pt 2):R514-8. doi: 10.1152/ajpregu.1997.272.2.R514.
This study was conducted to investigate a possible systemic effect of angiotensin-converting enzyme inhibitors (ACEi) on tissue antioxidant defenses. CF1 mice (4-mo-old females) were administered either water (control) or water containing enalapril (20 mg/l) or captopril (50 mg/l) during 11 wk. Neither enalapril nor captopril treatment had an effect on body mass or brain, kidney, or heart weight relative to controls. CuZn-superoxide dismutase (SOD) activity was increased by enalapril treatment in kidney medulla (27%), heart (24%), and erythrocytes (19%) and by captopril treatment in kidney medulla (43%) and heart (54%) relative to controls. Mn-SOD and catalase activities were unaffected by either treatment. Enalapril, but not captopril treatment, increased Se-glutathione peroxidase activity in renal medulla (19%). Nonenzymatic antioxidant defenses, evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (HICL), were enhanced in kidney cortex (48%) by enalapril and in brain by enalapril (44%) or captopril (36%) treatment relative to controls. As evaluated in vitro by HICL and thiobarbituric acid-reactive substances formation, captopril had a free radical scavenger activity, whereas neither enalapril nor lisinopril was effective. These results suggest that ACEi may protect tissues from oxidative damage by increasing enzymatic and nonenzymatic antioxidant defenses.
本研究旨在探讨血管紧张素转换酶抑制剂(ACEi)对组织抗氧化防御系统可能产生的全身影响。在11周内,给CF1小鼠(4月龄雌性)分别饮用纯水(对照组)或含依那普利(20 mg/L)或卡托普利(50 mg/L)的水。与对照组相比,依那普利和卡托普利治疗均未对体重、脑、肾或心脏重量产生影响。相对于对照组,依那普利治疗可使肾髓质(27%)、心脏(24%)和红细胞(19%)中的铜锌超氧化物歧化酶(SOD)活性增加,卡托普利治疗可使肾髓质(43%)和心脏(54%)中的SOD活性增加。两种治疗均未影响锰超氧化物歧化酶和过氧化氢酶的活性。依那普利治疗可使肾髓质中的硒谷胱甘肽过氧化物酶活性增加(19%),而卡托普利治疗则无此作用。通过叔丁基过氧化氢引发的化学发光法(HICL)评估的非酶抗氧化防御系统,依那普利可使肾皮质增强(48%),依那普利(44%)或卡托普利(36%)治疗可使脑增强。通过HICL和硫代巴比妥酸反应性物质形成在体外评估,卡托普利具有自由基清除活性,而依那普利和赖诺普利均无效。这些结果表明,ACEi可能通过增加酶促和非酶促抗氧化防御来保护组织免受氧化损伤。