普伐他汀提供抗氧化活性并保护负载伯氨喹的红细胞。
Pravastatin provides antioxidant activity and protection of erythrocytes loaded Primaquine.
机构信息
Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
出版信息
Int J Med Sci. 2010 Oct 28;7(6):358-65. doi: 10.7150/ijms.7.358.
Loading erythrocytes with Primaquine (PQ) is advantageous. However, PQ produces damage to erythrocytes through free radicals production. Statins have antioxidant action and are involved in protective effect against situation of oxidative stress. Thus the protective effect of pravastatin (PS) against PQ induced oxidative damage to human erythrocytes was investigated in the current studies upon loading to erythrocytes.The erythrocytes were classified into; control erythrocytes, erythrocytes incubated with either 2 mM of PS or 2 mM of PQ, and erythrocytes incubated with combination of PS plus PQ. After incubation for 30 min, the effect of the drugs on erythrocytes hemolysis as well as some biomarkers of oxidative stress (none protein thiols, protein carbonyl, thiobarbituric acid reactive substance) were investigated.Our results revealed that PS maintains these biomarkers at values similar to that of control ones. On the other hand, PQ cause significant increases of protein carbonyl by 115% and thiobarbituric acid reactive substance by 225% while non-protein thiols were significantly decreased by 112 % compared with control erythrocytes. PS pre-incubation before PQ exerts marked reduction of these markers in comparison with PQ alone. Moreover, at NaCl concentrations between 0.4% and 0.8%, PQ causes significant increase of Red Blood Cells (RBCs) hemolysis in comparison with the other groups (P<0. 001). Scanning electron micrograph indicates spherocytes formation by PQ incubation, but in the other groups the discocyte shape of erythrocytes was preserved.The reduction of protein oxidation and lipids peroxidation by PS is related to antioxidants effect of this statin. Preservation of erythrocytes fragility and morphology by PS are related to its free radicals scavenging effect. It is concluded that pravastatin has protective effect against erythrocytes dysfunction related any situations associated with increased oxidative stress, especially when loaded with PQ.
向红细胞中装载伯氨喹（PQ）是有利的。然而，PQ 通过自由基的产生对红细胞造成损伤。他汀类药物具有抗氧化作用，并参与对氧化应激情况的保护作用。因此，在本研究中，研究了普伐他汀（PS）在向红细胞中装载时对 PQ 诱导的人红细胞氧化损伤的保护作用。将红细胞分为：对照红细胞、用 2mM PS 或 2mM PQ 孵育的红细胞、以及用 PS 加 PQ 孵育的红细胞。孵育 30 分钟后，研究了药物对红细胞溶血以及一些氧化应激生物标志物（非蛋白巯基、蛋白羰基、硫代巴比妥酸反应性物质）的影响。
我们的结果表明，PS 将这些生物标志物保持在与对照值相似的水平。另一方面，PQ 导致蛋白羰基增加 115%，硫代巴比妥酸反应性物质增加 225%，而非蛋白巯基则比对照红细胞显著减少 112%。与单独使用 PQ 相比，PS 预先孵育后这些标志物的减少明显。此外，在 0.4%至 0.8%的 NaCl 浓度下，与其他组相比，PQ 导致 RBC 溶血显著增加（P<0.001）。扫描电子显微镜表明 PQ 孵育导致小球形红细胞的形成，但在其他组中红细胞保持圆盘形。PS 减少蛋白氧化和脂质过氧化与该他汀类药物的抗氧化作用有关。PS 对红细胞脆性和形态的保护与它的自由基清除作用有关。
综上所述，普伐他汀对与氧化应激增加相关的任何红细胞功能障碍都具有保护作用，特别是在与 PQ 一起装载时。
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