Aruoma O I, Akanmu D, Cecchini R, Halliwell B
Department of Biochemistry, University of London King's College, U.K.
Chem Biol Interact. 1991;77(3):303-14. doi: 10.1016/0009-2797(91)90039-a.
Captopril, an inhibitor of angiotensin-converting enzyme, has been suggested to have additional cardioprotective action because of its ability to act as an antioxidant. The rates of reaction of captopril with several biologically-relevant reactive oxygen species were determined. Captopril reacts slowly, if at all, with superoxide (rate constant less than 10(3) M-1 s-1) or hydrogen peroxide (rate constant less than M-1 s-1). It does not inhibit peroxidation of lipids stimulated by iron ions and ascorbate or by the myoglobin/H2O2 system. Indeed, mixtures of ferric ion and captopril can stimulate lipid peroxidation. Captopril reacts rapidly with hydroxyl radical (rate constant greater than 10(9) M-1 s-1) but might be unlikely to compete with most biological molecules for OH because of the low concentration of captopril that can be achieved in vivo during therapeutic use. Captopril did not significantly inhibit iron ion-dependent generation of hydroxyl radicals from hydrogen peroxide. By contrast, captopril is a powerful scavenger of hypochlorous acid: it was able to protect alpha 1-antiproteinase (alpha 1 AP) against inactivation by this species and to prevent formation of chloramines from taurine. We suggest that the antioxidant action of captopril in vivo is likely to be limited, and may be restricted to protection against damage by hypochlorous acid derived from the action of neutrophil myeloperoxidase.
卡托普利是一种血管紧张素转换酶抑制剂，因其具有抗氧化作用，有人认为它还具有额外的心脏保护作用。测定了卡托普利与几种具有生物学相关性的活性氧的反应速率。卡托普利与超氧阴离子（速率常数小于10³M⁻¹s⁻¹）或过氧化氢（速率常数小于M⁻¹s⁻¹）反应缓慢，甚至根本不反应。它不抑制铁离子和抗坏血酸或肌红蛋白/H₂O₂系统刺激的脂质过氧化。实际上，铁离子和卡托普利的混合物会刺激脂质过氧化。卡托普利与羟基自由基反应迅速（速率常数大于10⁹M⁻¹s⁻¹），但由于治疗使用期间体内可达到的卡托普利浓度较低，它可能不太可能与大多数生物分子竞争羟基自由基。卡托普利并未显著抑制铁离子依赖的过氧化氢产生羟基自由基的过程。相比之下，卡托普利是次氯酸的强力清除剂：它能够保护α1-抗蛋白酶（α1AP）不被该物质灭活，并防止牛磺酸形成氯胺。我们认为卡托普利在体内的抗氧化作用可能有限，可能仅限于保护免受中性粒细胞髓过氧化物酶作用产生的次氯酸的损伤。
