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Cardioprotective effects of losartan and diminazene against the ischemia/reperfusion injury in hyperthyroidism rats
Mosayeb Pashaei1,2, Mahvash Hesari1, Dareuosh Shackebaei1,3
1Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Canadian Journal of Physiology and Pharmacology
|February 20, 2024
Summary
Diminazene aceturate (DIZE) and its combination with losartan (LOS) protected against hyperthyroid cardiomyopathy in rats by improving cardiac function and reducing oxidative stress. LOS alone showed limited efficacy.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Hyperthyroidism, characterized by excess thyroid hormone, is a significant risk factor for developing heart disease.
- Cardiomyopathy is a serious complication of hyperthyroidism, leading to impaired heart function.
- Losartan (LOS) and diminazene aceturate (DIZE) have demonstrated cardioprotective properties in various cardiac conditions.
Purpose of the Study:
- To evaluate the cardioprotective effects of losartan (LOS), diminazene aceturate (DIZE), and their combination against levothyroxine (LT4)-induced cardiomyopathy in a rat model.
- To investigate the impact of these treatments on cardiac function, oxidative stress, and inflammatory markers in hyperthyroid rats.
Main Methods:
- Hyperthyroidism was induced in rats using levothyroxine (LT4) in drinking water for 28 days.
- Rats received oral administration of LOS (10 mg/kg) and/or subcutaneous administration of DIZE (15 mg/kg) for 28 days.
- Cardiac function was assessed using hemodynamic measurements, and biochemical markers of cardiac damage, oxidative stress, and inflammation were analyzed.
Main Results:
- DIZE and the combination therapy significantly reduced cardiac hypertrophy and levels of creatine kinase myoglobin and lactate dehydrogenase.
- Both DIZE and the combination therapy improved cardiac hemodynamic parameters, including left ventricular developed pressure (LVDP) and rate pressure product (RPP).
- DIZE reversed elevated tumor necrosis factor-alpha (TNF-α) levels, while LOS helped restore superoxide dismutase (SOD) activity, indicating reduced inflammation and oxidative stress.
Conclusions:
- Diminazene aceturate (DIZE), both alone and in combination with losartan (LOS), demonstrates significant cardioprotective effects against hyperthyroidism-induced cardiomyopathy in rats.
- The combination therapy and DIZE alone improved cardiac function and mitigated cardiac damage, oxidative stress, and inflammation.
- Losartan (LOS) monotherapy showed limited effectiveness in addressing the cardiac dysfunction induced by hyperthyroidism in this model.
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