S-limonene protects the heart in an experimental model of myocardial infarction induced by isoproterenol: Possible involvement of mitochondrial reactive oxygen species

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Rhana, Paula ; Barros, Guilherme Mendes ; Santos, Vinicius Cisneiros de Oliveira ; Costa, Alexandre Dantas ; dos Santos, Danillo Menezes ; Fernandes-Braga, Weslley ; Durco, Aimee Obolari ; Santos, Marcio Roberto Viana ; Roman-Campos, Danilo ; de Vasconcelos, Carla Maria Lins ; Cruz, Jader Santos ; Souza, Diego Santos

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 930, p. 11-pg., 2022-07-18.

Abstract

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 Ca2+, associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca2+ 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 Ca2+ and attenuation of oxidative stress via CaMKII. (AU)

• FAPESP's process: 19/18918-0 - Role of nitric oxide in cardiac arrhythmias during Hypothyroidism
• Grantee: Diego Santos de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
• Grantee: Danilo Roman Campos
• Support Opportunities: Regular Research Grants