The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats

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Author(s): Fadia A Mayyas*, Ahmad I Aljohmani, Karem H Alzoubi.

Journal Name: Current Molecular Pharmacology

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Aims: To examine the impact spironolactone on serum/cardiac aldosterone levels and some markers of myocardial oxidative status, inflammation and fibrosis in a rat model of hyperthyroidism.

Background: Hyperthyroidism promotes development and progression of cardiovascular diseases (CVDS). Aldosterone, a key mediator of myocardial inflammation, oxidative stress and fibrosis, may be activated in hyperthyroidism.

Objective: To assess the impact of hyperthyroidism on aldosterone levels and myocardial oxidative status, inflammatory and fibrotic markers in hyperthyroid rats, and to test if use of spironolactone (an aldosterone antagonist) will attenuate these changes.

Method: Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0.3mg/kg/day), and spironolactone treated hyperthyroid rats (Hyper+Spir) for 4 weeks. Levels of blood pressure (Bp), serum and myocardial aldosterone, oxidants/antioxidants, inflammatory and fibrotic markers were measured.

Result: Levothyroxine increased serum thyroid hormones and increased Bp, heart rate and heart to body weight ratio. Relative to control, serum aldosterone levels were increased in Hyper and Hyper+Spir groups. In parallel, cardiac lipid peroxides and serum endothelin-1 were increased whereas cardiac super oxide dismutase, catalase, glutathione, and matrix metalloproteinase -2 were reduced in Hyper group. Spironolactone decreased serum thyroid hormones and improved cardiac lipid peroxides and metalloproteinase -2 levels. Use of spironolactone decreased serum nitrite levels and increased cardiac SOD and glutathione. Cardiac levels of aldosterone, endothelin-1, transforming growth factor beta and nitrite were similar among all groups.

Conclusion: Hyperthyroid status was associated with an increase in aldosterone and oxidant/inflammatory biomarkers. Use of spironolactone enhanced antioxidant defenses and reduced thyroid hormones. Aldosterone antagonists may serve as potential drugs to attenuate development of cardiac disease in hyperthyroidism.

Keywords: Spironolactone, Hyperthyroidism, Aldosterone, Fibrosis, Inflammation., Cardiovascular disease, Oxidative stress

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1874467212666191113150553
Price: $95