Mayyas Fadia, Alzoubi Karem H, Bonyan Ruwidah
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Cardiovasc Ther. 2017 Apr;35(2). doi: 10.1111/1755-5922.12242.
Diabetes mellitus (DM) is linked to cardiovascular diseases development and progression. Aldosterone contributes to cardiac oxidative stress and remodeling.
To evaluate the impact of spironolactone (an aldosterone antagonist) on markers of myocardial redox status in a rat model of streptozotocin (STZ)-induced DM.
Adult Sprague Dawley rats were randomized into four groups; controls, spironolactone-treated rats (Spir), diabetic rats (DM), and diabetic rats treated with spironolactone (DM+Spir) for 4 weeks. Blood pressure and cardiac levels of aldosterone and oxidants/antioxidants were measured.
STZ-induced DM but did not cause hypertension or dyslipidemia in either spironolactone-treated or spironolactone-untreated rats. Aldosterone and aldosterone synthase levels were increased in both the DM and DM+Spir groups compared to control. In parallel, total nitrite and nitrotyrosine levels were increased and vitamin E antioxidant levels were reduced in the DM group. Spironolactone use reduced cardiac total nitrite levels and improved vitamin E levels. Glutathione reductase/peroxidase activities were increased in the DM and DM+Spir groups without changes in the ratio of reduced to oxidized form of glutathione. Superoxide dismutase (SOD) and catalase activities were increased in the DM group. Lipid peroxidation products were similar among the groups.
The increase in total nitrite/nitrotyrosine in DM promoted significant compensatory increases in antioxidant activities of SOD, catalase and glutathione peroxidase/reductase probably to prevent cardiac oxidative damage. The use of spironolactone reduced nitrite generation and improved vitamin E levels independent of blood pressure.
糖尿病（DM）与心血管疾病的发生和发展有关。醛固酮会导致心脏氧化应激和重塑。
评估螺内酯（一种醛固酮拮抗剂）对链脲佐菌素（STZ）诱导的糖尿病大鼠模型中心肌氧化还原状态标志物的影响。
将成年Sprague Dawley大鼠随机分为四组；对照组、接受螺内酯治疗的大鼠（Spir）、糖尿病大鼠（DM）以及接受螺内酯治疗的糖尿病大鼠（DM+Spir），为期4周。测量血压以及心脏中醛固酮和氧化剂/抗氧化剂的水平。
STZ诱导了糖尿病，但在接受螺内酯治疗或未接受螺内酯治疗的大鼠中均未引起高血压或血脂异常。与对照组相比，DM组和DM+Spir组的醛固酮和醛固酮合酶水平均升高。同时，DM组的总亚硝酸盐和硝基酪氨酸水平升高，维生素E抗氧化剂水平降低。使用螺内酯可降低心脏总亚硝酸盐水平并提高维生素E水平。DM组和DM+Spir组的谷胱甘肽还原酶/过氧化物酶活性增加，而谷胱甘肽还原型与氧化型的比例没有变化。DM组的超氧化物歧化酶（SOD）和过氧化氢酶活性增加。各组间脂质过氧化产物相似。
DM中总亚硝酸盐/硝基酪氨酸的增加可能促使SOD、过氧化氢酶和谷胱甘肽过氧化物酶/还原酶的抗氧化活性显著代偿性增加，以预防心脏氧化损伤。使用螺内酯可降低亚硝酸盐生成并提高维生素E水平，且与血压无关。
