SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats
Nermeen Bastawy1, Aliaa E M K El-Mosallamy2, Samira H Aljuaydi3
1Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Abstract:
Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA's potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.
Insights
Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I), like dapagliflozin, show promise in treating hyperthyroidism-related heart and lung damage. This study found SGLT2-I effectively reduced inflammation and improved cardiac function in rats with induced hyperthyroidism.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Hyperthyroidism can lead to serious cardiac complications.
- Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) are known for their cardio-protective effects in heart failure.
Purpose of the Study:
- To investigate the therapeutic potential of SGLT2-I, specifically dapagliflozin (DAPA), on hyperthyroidism-induced cardiopulmonary injury.
- To explore the underlying mechanisms of DAPA's effects in a rat model.
Main Methods:
- Rats were induced with hyperthyroidism using LT4 and treated with DAPA.
- Evaluations included body weight, ECG, serum hormones, redox balance, DNA fragmentation, inflammatory cytokines (TNF-α, IGF-1), and mtTFA.
- Histological and immunohistochemical analyses of heart and lung tissues were performed.
Main Results:
- DAPA treatment restored serum biomarkers, improved ECG, and reinstated redox balance in hyperthyroid rats.
- DAPA reduced DNA fragmentation, increased mtTFA, and decreased TNF-α and IGF-1 gene expression.
- Histological examination showed DAPA improved necro-inflammatory and fibrotic changes, reducing TNF-α and caspase-3 expression.
Conclusions:
- Dapagliflozin demonstrates potential in alleviating hyperthyroidism-induced cardiopulmonary injury in rats.
- The protective effects are attributed to antioxidant, anti-inflammatory, and anti-apoptotic actions, and antagonism of sympathetic overactivity.
- Further clinical studies are needed to confirm these findings in humans.
Related Concept Videos
01:26Heart Failure Drugs: Inotropic Agents
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System