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他汀类药物体外抗氧化活性的比较研究。

A comparative study of the in vitro antioxidant activity of statins.

作者信息

Franzoni Ferdinando, Quiñones-Galvan Alfredo, Regoli Francesco, Ferrannini Ele, Galetta Fabio

机构信息

Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, 56100 Pisa, Italy.

出版信息

Int J Cardiol. 2003 Aug;90(2-3):317-21. doi: 10.1016/s0167-5273(02)00577-6.

Abstract

BACKGROUND

Treatment of hypercholesterolemia with statins is remarkably effective in cardiovascular prevention. This has led to the hypothesis that these drugs may act on the atherosclerotic plaque by mechanism(s) independent of the reduction of serum cholesterol levels. The aim of this study was to assess the total antioxidant activity of the most prescribed statins: fluvastatin, atorvastatin, pravastatin and simvastatin.

METHODS

We measured the in vitro antioxidant activity of statins as their ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Uric acid and Trolox were used as the reference antioxidants.

RESULTS

The scavenging capacity towards hydroxyl radicals was highest for simvastatin (3375+/-112 U/mg), a value 270.2% higher (P<0.0001) compared to uric acid (reference antioxidant vs. hydroxyl radicals, 1249+/-71 U/mg). Among the tested statins, fluvastatin exhibited the highest anti-peroxyl radical antioxidant capacity (8755+/-187 U/mg) which appeared 50% lower (P<0.0001) compared to Trolox (reference antioxidant vs. peroxyl radicals, 17460+/-379 U/mg).

CONCLUSIONS

All the statins tested have intrinsic antioxidant activity with both anti-hydroxyl and peroxyl radical activity. Simvastatin was the most effective as an anti-hydroxyl radical antioxidant and fluvastatin as an anti-peroxyl radical antioxidant.

摘要

背景

他汀类药物治疗高胆固醇血症在心血管预防方面效果显著。这引发了一种假说,即这些药物可能通过独立于降低血清胆固醇水平的机制作用于动脉粥样硬化斑块。本研究的目的是评估最常用的他汀类药物:氟伐他汀、阿托伐他汀、普伐他汀和辛伐他汀的总抗氧化活性。

方法

我们测量了他汀类药物的体外抗氧化活性,即它们拮抗α-酮-γ-甲硫基丁酸被羟基自由基和过氧自由基氧化的能力。结果以总氧自由基清除能力(TOSC)单位表示。尿酸和Trolox用作参考抗氧化剂。

结果

辛伐他汀对羟基自由基的清除能力最高(3375±112 U/mg),与尿酸(参考抗氧化剂对羟基自由基,1249±71 U/mg)相比,该值高270.2%(P<0.0001)。在测试的他汀类药物中,氟伐他汀表现出最高的抗过氧自由基抗氧化能力(8755±187 U/mg),与Trolox(参考抗氧化剂对过氧自由基,17460±379 U/mg)相比,该值低50%(P<0.0001)。

结论

所有测试的他汀类药物都具有内在的抗氧化活性,兼具抗羟基自由基和抗过氧自由基活性。辛伐他汀作为抗羟基自由基抗氧化剂最有效,氟伐他汀作为抗过氧自由基抗氧化剂最有效。

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