ABSTRACT
Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups: sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.
Subject(s)
Autonomic Nervous System/physiopathology , Heart Diseases/therapy , Heart/innervation , Physical Conditioning, Animal , Resistance Training , Animals , Baroreflex/drug effects , Cardiotoxicity , Disease Models, Animal , Doxorubicin , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/physiopathology , Hemodynamics/drug effects , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Ventricular Function, Left/drug effectsABSTRACT
Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.
Subject(s)
Antioxidants/therapeutic use , Apoptosis/drug effects , Limonene/therapeutic use , Myocardial Infarction/drug therapy , Reactive Oxygen Species/metabolism , Animals , Apoptosis Regulatory Proteins/drug effects , Apoptosis Regulatory Proteins/metabolism , Electrocardiography/drug effects , Long QT Syndrome/prevention & control , Male , Mice , Molecular Structure , Oxidative Stress/drug effects , Superoxide Dismutase/metabolismABSTRACT
Nerol (C10H18O) is a monoterpene found in many essential oils, such as lemon balm and hop. In this study, we explored the contractile and electrophysiological properties of nerol and demonstrated its antiarrhythmic effects in guinea pig heart preparation. Nerol effects were evaluated on atrial and ventricular tissue contractility, electrocardiogram (ECG), voltage-dependent L-type Ca2+ current (ICa,L), and ouabain-triggered arrhythmias. Overall our results revealed that by increasing concentrations of nerol (from 0.001 to 30 mM) there was a significant decrease in left atrium contractile force. This effect was completely and rapidly reversible after washing out (~ 2 min). Nerol (at 3 mM concentration) decreased the left atrium positive inotropic response evoked by adding up CaCl2 in the extracellular medium. Interestingly, when using a lower concentration of nerol (30 µM), it was not possible to clearly observe any significant ECG signal alterations but a small reduction of ventricular contractility was observed. In addition, 300 µM nerol promoted a significant decrease on the cardiac rate and contractility. Important to note is the fact that in isolated cardiomyocytes, peak ICa,L was reduced by 58.9 ± 6.31% after perfusing 300 µM nerol (n=7, p<0.05). Nerol, at 30 and 300 µM, delayed the time of onset of ouabain-triggered arrhythmias and provoked a decrease in the diastolic tension induced by the presence of ouabain (50 µM). Furthermore, nerol preincubation significantly attenuated arrhythmia severity index without changes in the positive inotropism elicited by ouabain exposure. Taken all together, we may be able to conclude that nerol primarily by reducing Ca2+ influx through L-type Ca2+ channel blockade lessened the severity of ouabain-triggered arrhythmias in mammalian heart.
