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

Mayyas, Fadia; Aljohmani, Ahmad; Alzoubi, Karem H.

doi:10.2174/1874467212666191113150553

Cited by 7 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a hyperthyroid Wistar rat model induced by intraperitoneal injection with exogenous thyroxine for 4 weeks, cardiac lipid peroxides and serum endothelin-1 were increased, whereas cardiac superoxide dismutase, catalase, glutathione, and matrix metalloproteinase-2 were reduced in the hyperthyroid group. Unfortunately, myocardial inflammation (MPO level) and fibrosis (Masson trichrome staining) did not change significantly compared with the controls ( 57 ). Interestingly, hypothyroidism rats seem to be related with significant sterile inflammatory changes (leukocyte infiltration) in cardiac tissue ( 58 ).…”

Section: Discussionmentioning

confidence: 89%

Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review

Wang

Leng

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The manifestations of hyperthyroidism-related myocardial damage are multitudinous, including arrhythmia, dilated cardiomyopathy, valvular diseases, and even cardiogenic shock. Acute myocarditis induced by thyrotoxicosis had been reported in a few studies. However, attention on its prevalence and underlying mechanisms is sorely lacking. Its long-term harm is often ignored, and it may eventually develop into dilated cardiomyopathy and heart failure. We report a case of Graves' disease with a progressive elevation of hypersensitive cardiac troponin-I at several days after discontinuation of the patient's anti-thyroid drugs. Cardiac magnetic resonance imaging (CMRI) showed inflammatory edema of some cardiomyocytes (stranded enhanced signals under T2 mapping), myocardial necrosis (scattered enhanced signals under T1 late gadolinium enhancement) in the medial and inferior epicardial wall, with a decreased left ventricular systolic function (48%), which implied a possibility of acute myocarditis induced by thyrotoxicosis. The patient was then given a transient glucocorticoid (GC) treatment and achieved a good curative effect. Inspired by this case, we aim to systematically elaborate the pathogenesis, diagnosis, and treatment of hyperthyroidism-induced autoimmune myocarditis. Additionally, we emphasize the importance of CMRI and GC therapy in the diagnosis and treatment of hyperthyroidism-related myocarditis.

show abstract

Section: Discussionmentioning

confidence: 89%

Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review

Wang

Leng

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…It has been shown that spironolactone exhibits antioxidant activity and protects organs against oxidative stress by inhibiting the production of free radicals [69]. There is also a substantial amount of evidence from animal models that spironolactone can play a role in the reduction in oxidative stress and antioxidant defenses, e.g., in hyperthyroid rats [75]. Moreover, spironolactone has long been shown to inhibit aldosterone-induced oxidative stress in human endothelial cells [76].…”

Section: Oxidative Stressmentioning

confidence: 99%

COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

et al. 2021

View full text Add to dashboard Cite

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

show abstract

“…However, its use particularly at higher dose has been associated with intermenstrual bleeding due to reduction in production of estradiol and endometrial thickness [23,24]. Interestingly, a number of studies, including recent studies from our laboratory animals have demonstrated the effectiveness and safety of low-dose SPL against endocrine disruption in PCOS models [25][26][27][28]. However, the effects of low-dose SPL on PCOS-associated adipose dysfunction is unknown.…”

Section: Introductionmentioning

confidence: 99%

Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model

et al. 2022

View full text Add to dashboard Cite

Background of study Globally, many reproductive aged women are affected by polycystic ovarian syndrome (PCOS), which is a common endocrine and metabolic disorder that is linked with adipose dysfunction and chronic low-grade inflammation. Spironolactone (SPL), a mineralocorticoid receptor blocker has been documented as a metabolic modulator. However, its immunomodulatory effect in PCOS is unknown. Therefore, the present study hypothesized that SPL would ameliorate adipose dysfunction and inflammation in experimental PCOS animals. Materials and methods Female Wistar rats that were 8 weeks old were allocated into three groups. Group 1 received vehicle (distilled water; p.o.), group 2 received letrozole (1 mg/kg; p.o.) and group 3 received letrozole plus SPL (0.25 mg/kg, p.o.). The administration was performed once daily for 21 days. Results The experimental PCOS animals showed insulin resistance, hyperinsulinemia and hyperandrogenism as well as oxidative stress and elevated inflammatory biomarkers (NF-kB/TNF-/IL-6) as well as a significant decrease in triglycerides, total cholesterol, free fatty acids, GSH and G6PD in the adipose tissue of PCOS animals. In addition, immunohistochemical assessment of adipose tissue showed significant expression of BAX and inflammasome, indicating apoptosis and inflammation compared to control animals. Nevertheless, administration of SPL attenuated these perturbations. Conclusion Altogether, the present study suggests that low-dose spironolactone confers protection against adipose dysfunction in experimental PCOS animals by attenuating inflammation, oxidative stress and cellular apoptosis.

show abstract

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

Cited by 7 publications

References 46 publications

Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review

Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review

COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model

Contact Info

Product

Resources

About