Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors
Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors
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DOI：
10.3164/jcbn.18-48
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Tokumaru, Osamu
中科院分区：
文献类型：
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作者：
Umeda, Ryohei;Takanari, Hiroki;Tokumaru, Osamu
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，即他汀类药物，广泛用于通过控制血液胆固醇水平来预防心脑血管疾病。此外，先前的研究揭示了他汀类药物对自由基的清除作用。我们利用电子自旋共振光谱法和自旋俘获法评估了两种水溶性他汀类药物氟伐他汀和普伐他汀对多种自由基的直接清除活性。我们估计了反应速率常数（氟伐他汀的k（fv）和普伐他汀的k(pv)）。氟伐他汀和普伐他汀对超氧阴离子的清除作用，k（fv）为4.82 M(-1)s(-1), k（pv）为49.0 M(-1)s（-1）。氟伐他汀和普伐他汀对羟基自由基的清除作用具有可比性；k（fv）和k（pv）都是bbb10 (9) M(-1)s（-1）氟伐他汀也能消除叔丁基过氧基自由基，相对k（fv）为2.63，而普伐他汀对叔丁基过氧基自由基无影响。氟伐他汀和普伐他汀清除一氧化氮的k（fv）和k（pv）分别为68.6 M(-1)s（-1）和701 M(-1)s（-1）。氟伐他汀和普伐他汀对超氧阴离子、羟基自由基和一氧化氮自由基均有清除作用。另一方面，氟伐他汀仅能清除叔丁基过氧基自由基，提示氟伐他汀可能比普伐他汀更能通过抑制脂质氧化来预防动脉粥样硬化和缺血再灌注损伤。
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (k(fv) for fluvastatin, and k(pv) for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with k(fv) and k(pv) of 4.82 M(-1)s(-1) and 49.0 M(-1)s(-1), respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both k(fv), and k(pv), were >10(9) M(-1)s(-1). Fluvastatin also eliminated tertbutyl peroxyl radical with relative k(fv), of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with k(fv), and k(pv) of 68.6 M(-1)s(-1) and 701 M(-1)s(-1), respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tertbutyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.