Department of Physiology and Membrane Biology, University of California Davis, Davis, USA; Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Eur J Pharmacol. 2022 Sep 5;930:175134. doi: 10.1016/j.ejphar.2022.175134. Epub 2022 Jul 14.
Myocardial infarction (MI) is associated with high mortality rates, despite the fact that there are therapies available. Importantly, excessive oxidative stress may contribute to ischemia/reperfusion injury leading to death related to MI. In this scenario, naturally occurring antioxidant compounds are an important source of possible therapeutic intervention. Thus, this study sought to elucidate the mechanisms of cardioprotection of s-limonene in an isoproterenol-induced MI animal model.
Wistar rats were treated with 1 mg/kg s-limonene (SL) or 100 mg/kg N-acetylcysteine (NAC, positive control) once, 30 min after isoproterenol-induced MI (applied in two doses with a 24 h interval). The protective effects of SL in the heart were examined via the serum level of creatine kinase myocardial band (CK-MB), electrocardiographic profile, infarct size and histological parameters. Using isolated cardiomyocytes, we also assessed calcium transient amplitude, cytosolic and mitochondrial oxidative stress and the expression of proteins related to oxidative stress.
SL at a concentration of 1 mg/kg attenuated isoproterenol-induced MI injury, by preventing ST-segment elevation and QTc prolongation in the ECG. SL reduced the infarct size and collagen content in cardiac tissue. At the cellular level, SL prevented increased Ca, associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca Calmodulin-Dependent Kinase II (CaMKII) and restored superoxide dismutase and glutathione peroxidase activity.
Our data show that s-limonene promotes cardioprotection against MI injury, probably through inhibition of increased Ca and attenuation of oxidative stress via CaMKII.
心肌梗死（MI）尽管有治疗方法，但死亡率仍然很高。重要的是，过度的氧化应激可能导致与 MI 相关的缺血/再灌注损伤。在这种情况下，天然抗氧化化合物是可能的治疗干预的重要来源。因此，本研究旨在阐明在异丙肾上腺素诱导的 MI 动物模型中，柠檬烯的心脏保护机制。
Wistar 大鼠在异丙肾上腺素诱导的 MI（24 小时间隔两次给予）后 30 分钟，给予 1mg/kg 的柠檬烯（SL）或 100mg/kg 的 N-乙酰半胱氨酸（NAC，阳性对照）一次。通过血清肌酸激酶同工酶 MB（CK-MB）水平、心电图谱、梗死面积和组织学参数检查 SL 在心脏中的保护作用。使用分离的心肌细胞，我们还评估了钙瞬变幅度、细胞质和线粒体氧化应激以及与氧化应激相关的蛋白质的表达。
浓度为 1mg/kg 的 SL 通过防止心电图中的 ST 段抬高和 QTc 延长，减轻了异丙肾上腺素诱导的 MI 损伤。SL 减少了心脏组织中的梗死面积和胶原蛋白含量。在细胞水平上，SL 防止了 Ca 的增加，与细胞质和线粒体氧化应激的减弱有关。这些变化导致 Ca 钙调蛋白依赖性激酶 II（CaMKII）的氧化形式减少，并恢复了超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。
我们的数据表明，柠檬烯通过抑制 Ca 的增加和通过 CaMKII 减弱氧化应激来促进对 MI 损伤的心脏保护作用。
