Myrtenol protects against myocardial ischemia-reperfusion injury through antioxidant and anti-apoptotic dependent mechanisms

• Published in: Food and chemical toxicology Vol. 111; pp. 557 - 566
• Main Authors: Britto, Raquel Moreira de, Silva-Neto, Júlio Alves da, Mesquita, Thássio Ricardo Ribeiro, Vasconcelos, Carla Maria Lins de, de Almeida, Grace Kelly Melo, Jesus, Itamar Couto Guedes de, Santos, Péligris Henrique dos, Souza, Diego Santos, Miguel-dos-Santos, Rodrigo, de Sá, Lucas Andrade, dos Santos, Fanildes Silva Moraes, Pereira-Filho, Rose Nely, Albuquerque-Júnior, Ricardo Luiz Cavalcanti, Quintans-Júnior, Lucindo José, Guatimosim, Silvia, Lauton-Santos, Sandra
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2018
• Subjects: Apoptosis; Ischemia-reperfusion; Monoterpenes; Myocardial injury; Myrtenol; Oxidative stress; Ischemia-reperfusion; Oxidative stress; Monoterpenes; Myrtenol; Myocardial injury; Apoptosis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2017.12.003

Myrtenol is a monoterpene with multiple pharmacological activities. However, although monoterpenes have been proposed to play beneficial roles in a variety of cardiac disorders, pharmacological actions of myrtenol in the heart are not yet reported. Hence, the aim of this study was to evaluate whether myrtenol promotes cardioprotection against myocardial ischemia-reperfusion (IR) injury, and the mechanisms involved in these effects. Male Wistar rats were orally treated for seven consecutive days with myrtenol (50 mg/kg) or N-acetyl cysteine (1.200 mg/kg, NAC). Afterward, hearts were subjected to myocardial IR injury. Here, we show that the severe impairment of contractile performance induced by IR was significantly prevented by myrtenol or NAC. Moreover, myrtenol abolished aberrant electrocardiographic waveform (ST-segment elevation), as well as reduced life-threatening arrhythmias and infarct size induced by IR injury. Importantly, myrtenol fully prevented the massive increase of cardiac reactive oxygen species generation and oxidative stress damage. Accordingly, myrtenol restored the impairment of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and reductase) activities and balance of pro- and anti-apoptotic pathways (Bax and Bcl-2), associated with decreased apoptotic cells. Taken together, our data show that myrtenol promotes cardioprotection against IR injury through attenuation of oxidative stress and inhibition of pro-apoptotic pathway. •Myrtenol treatment (50 mg/kg/day 7 days) prevents the ventricular dysfunction induced by IR injury.•The remarkable cardioprotection of myrtenol was associated with reduction of arrhythmias and myocardial infarct size.•Myrtenol protects hearts against IR-induced injury via inhibition of oxidative stress and pro-apoptotic-dependent pathways.