RESUMEN
Ischemia-reperfusion (I/R) injury causes oxidative stress, leading to severe cardiac dysfunction. Thus, biologically active compounds with antioxidant properties may be viewed as a promising therapeutic strategy against oxidative-related cardiac disorders. Usnic acid (UA), a natural antioxidant, was complexed with ß-cyclodextrin (ßCD) to improve its bioavailability. Wistar male rats were orally treated with the free form of UA (50 mg/kg) or the inclusion complex UA/ßCD (50 mg/kg) for seven consecutive days. Afterward, hearts were subjected to I/R injury, and the cardiac contractility, rhythmicity, infarct size, and antioxidant enzyme activities were evaluated. Here, we show that neither UA nor UA/ßCD treatments developed signs of toxicity. After I/R injury, animals treated with UA/ßCD showed improved post-ischemic cardiac functional recovery while the release of cell injury biomarkers decreased. Following reduced cardiac damage, a lower incidence of ventricular arrhythmias and smaller myocardial infarct size were associated with reduced lipid peroxidation, along with preserved activity of antioxidant enzymes compared to untreated rats. Surprisingly, uncomplexed UA did not protect hearts against IR injury. Altogether, our results indicate that the inclusion complex UA/ßCD is a critical determining factor responsible for the cardioprotection action of UA, suggesting the involvement of an antioxidant-dependent mechanisms. Moreover, our findings support that UA/ßCD is a structurally engineered compound with active cardioprotective properties.
Asunto(s)
Benzofuranos/farmacología , Cardiotónicos/farmacología , beta-Ciclodextrinas/química , Animales , Benzofuranos/química , Benzofuranos/uso terapéutico , Cardiotónicos/química , Cardiotónicos/uso terapéutico , Masculino , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , TermogravimetríaRESUMEN
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.