Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects
Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects
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DOI：
10.1111/nmo.12404
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发表时间：
2014-10-01
影响因子：
3.5
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
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作者：
Bharucha, Adil E.;Choi, Kyoung Moo;Zinsmeister, Alan R.
背景血红素加氧酶1（HO-1）降解血红素并对抗氧化应激。体外和动物模型表明，HO-1在几种疾病中是有益的（例如，例如，在一个实施例中，术后肠梗阻、胃轻瘫、急性胰腺炎和结肠炎）。然而，唯一的药物（i。例如，血红素和精氨酸血红素）是昂贵的，并且只能静脉内给药。我们的目的是比较安慰剂、阿司匹林和辛伐他汀单独使用以及与α-硫辛酸联合使用对人体HO-1蛋白浓度和活性的影响。方法采用随机、双盲、安慰剂对照的研究方法，比较3种口服方案治疗7 d的疗效。例如，安慰剂;阿司匹林（325 mg，每日两次）和辛伐他汀（40 mg，每日两次）;阿司匹林、辛伐他汀和R-α-硫辛酸钠盐（NaRLA，600 mg，每日三次）对HO-1活化标志物的影响（i.例如，血浆HO-1蛋白浓度和静脉单核细胞HO-1蛋白活性）。在基线、第2天和第7天评价HO-1活化标志物。关键结果基线HO-1蛋白浓度和活性在三组中相似。与安慰剂相比，阿司匹林和辛伐他汀联合或与NaRLA一起在2或7天时不影响HO-1蛋白浓度或活性。HO-1蛋白浓度和活性在第7天相关（r = 0.75，p = 0.0004），但在基线和第2天不相关。结论和推论在治疗剂量下，阿司匹林、辛伐他汀和α-硫辛酸不会增加健康人血浆HO-1蛋白浓度或静脉单核细胞HO-1活性。
Background Heme oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e. g., postoperative ileus, gastroparesis, acute pancreatitis, and colitis). However, the only drugs (i. e., hemin and heme arginate) which pharmacologically upregulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin, and simvastatin alone, and with a-lipoic acid, on HO-1 protein concentration and activity in humans. Methods This randomized, double-blind, placebo-controlled study compared the effects of three oral regimens administered for 7 days, i. e., placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R-a-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i. e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2, and 7. Key Results Baseline HO-1 protein concentrations and activity were similar among the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2. Conclusions & Inferences At therapeutic doses, aspirin, simvastatin, and a-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans.