Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Can J Physiol Pharmacol. 2024 Jun 1;102(6):383-390. doi: 10.1139/cjpp-2023-0122. Epub 2024 Feb 20.
Hyperthyroidism is a condition where the thyroid gland produces high levels of thyroid hormone. Heart diseases are one of the main complications of hyperthyroidism. Several studies have shown that losartan (LOS) and diminazene aceturate (DIZE) possess cardioprotection effects against cardiac hypertrophy, ischemic heart disease, and heart failure. The research aimed to investigate the cardioprotection of LOS, DIZE, and their combination in the case of levothyroxine (LT4)-induced cardiomyopathy in rats. Hyperthyroidism was induced by LT4 in drinking water (12 mg/L) for 28 days. LOS (10 mg/kg, orally) and/or DIZE (15 mg/kg, subcutaneously) were administrated in rats with hyperthyroidism for 28 days. Decreased serum creatine kinase myoglobin and lactate dehydrogenase levels and cardiac hypertrophy by DIZE and combination therapy in hyperthyroidism rats have been reported. Cardiac hemodynamic findings showed that DIZE and its combination with LOS decreased the LT4-mediated left ventricular developed pressure (LVDP), rate pressure product (RPP), and RPP recovery percentage. Elevated cardiac oxidative stress and inflammation were confirmed by decreasing cardiac superoxide dismutase (SOD) activity and increasing the total oxidative stress and tumor necrosis factor-alpha (TNF-α) levels. SOD activity and TNF-α level were reversed by LOS and DIZE administration, respectively. Generally, DIZE and combination therapy with LOS improved cardiac dysfunction caused by hyperthyroidism in rats, whereas LOS alone has not been able to effectively respond to this dysfunction.
甲状腺功能亢进症是甲状腺产生高水平甲状腺激素的一种疾病。心脏病是甲状腺功能亢进症的主要并发症之一。几项研究表明，氯沙坦（LOS）和米氮平（DIZE）对心肌肥厚、缺血性心脏病和心力衰竭具有心脏保护作用。本研究旨在探讨 LOS、DIZE 及其联合应用在左旋甲状腺素（LT4）诱导的大鼠心肌病中的心脏保护作用。通过在饮用水中（12mg/L）给予 LT4 28 天诱导甲状腺功能亢进症。在甲状腺功能亢进症大鼠中给予 LOS（10mg/kg，口服）和/或 DIZE（15mg/kg，皮下）28 天。据报道，DIZE 及其与 LOS 的联合治疗可降低甲状腺功能亢进症大鼠的血清肌酸激酶肌红蛋白和乳酸脱氢酶水平和心肌肥厚。心脏血流动力学研究结果表明，DIZE 及其与 LOS 的联合应用降低了 LT4 介导的左心室发展压（LVDP）、压力速率产物（RPP）和 RPP 恢复百分比。心脏超氧化物歧化酶（SOD）活性降低和总氧化应激以及肿瘤坏死因子-α（TNF-α）水平升高证实了心脏氧化应激和炎症的升高。LOS 和 DIZE 的给药分别逆转了 SOD 活性和 TNF-α水平。总的来说，DIZE 和与 LOS 的联合治疗改善了大鼠甲状腺功能亢进引起的心脏功能障碍，而 LOS 单独治疗未能有效应对这种功能障碍。
