| アブストラクト | BACKGROUND: 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. METHODS: 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. RESULTS: 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(2+), associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca(2+) Calmodulin-Dependent Kinase II (CaMKII) and restored superoxide dismutase and glutathione peroxidase activity. CONCLUSION: Our data show that s-limonene promotes cardioprotection against MI injury, probably through inhibition of increased Ca(2+) and attenuation of oxidative stress via CaMKII. |
| ジャーナル名 | European journal of pharmacology |
| 投稿日 | 2022/7/18 |
| 投稿者 | Rhana, Paula; Barros, Guilherme Mendes; Santos, Vinicius Cisneiros de Oliveira; Costa, Alexandre Dantas; Santos, Danillo Menezes Dos; Fernandes-Braga, Weslley; Durco, Aimee Obolari; Santos, Marcio Roberto Viana; Roman-Campos, Danilo; Vasconcelos, Carla Maria Lins de; Cruz, Jader Santos; Souza, Diego Santos |
| 組織名 | 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, Sao Cristovao, Brazil.;Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo;Horizonte, Brazil.;Department of Physiology, Federal University of Sergipe, Sao Cristovao, Brazil;;Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil.;Department of Biochemistry and Immunology, Federal University of Minas Gerais,;Belo Horizonte, Brazil.;Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil.;Electronic address: carlamlv@hotmail.com.;Belo Horizonte, Brazil. Electronic address: jader@icb.ufmg.br.;Electronic address: santos.dss@outlook.com. |
| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/35843301/ |