RESUMEN
Wogonin is a flavonoid isolated from Scutellaria baicalensis Georgi, a traditional Chinese medicine, and it possesses antioxidant and anti-inflammatory effects. The aim of this study is to investigate the in vivo effect of wogonin on myocardial ischemia/reperfusion injury in an open-chest anesthetized rat model, which was induced by 45-minute left coronary artery occlusion and 2-hour reperfusion. Rats were treated with wogonin (5, 10, and 20 mg/kg, intraperitoneal) 40 minutes before ischemia or treatment with 10 mg/kg of wogonin 15 minutes after occlusion. Pretreatment with 10 mg/kg of wogonin significantly delayed the occurrence of ventricular premature contractions and tachycardia, and it suppressed the incidence of ventricular tachycardia and ventricular fibrillation, and mortality elicited by ischemia when compared with that in the control group, accompanied by reducing the arrhythmia scores. After 2-hour reperfusion, pretreatment and posttreatment with wogonin significantly reduced the infarct size and plasma levels of creatine kinase muscle-brain fraction and lactate dehydrogenase. Wogonin also significantly reduced the elevation of plasma tissue necrosis factor-α and superoxide anion production in the myocardium with ischemia/reperfusion. The expression of monocyte chemoattractant protein-1, phosphorylated p38 mitogen-activated protein kinase, p65 and IκBα, and active caspase-3 in ischemic myocardium pronouncedly increased in the control group; these were significantly attenuated by treatment with wogonin. In conclusion, wogonin demonstrated in vivo cardioprotective effects by the attenuation of the severity of ischemia-induced arrhythmias and irreversible ischemia/reperfusion injury, which is associated with its antioxidant capacity and anti-inflammatory effects. The suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation and the inhibition of monocyte chemoattractant protein-1 expression contribute to the beneficial effects of wogonin.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Apoptosis/efectos de los fármacos , Arritmias Cardíacas/tratamiento farmacológico , Flavanonas/uso terapéutico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Arritmias Cardíacas/etiología , Arritmias Cardíacas/inmunología , Arritmias Cardíacas/patología , Western Blotting , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/inmunología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Flavanonas/administración & dosificación , Hemodinámica/efectos de los fármacos , Masculino , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/inmunología , Daño por Reperfusión Miocárdica/patología , FN-kappa B/biosíntesis , FN-kappa B/inmunología , Ratas , Ratas Sprague-Dawley , Superóxidos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
AIM OF THE STUDY: To evaluate the protective effect of baicalein on myocardial dysfunction caused by endotoxaemia in rats and to explore the possible mechanisms. MATERIALS AND METHODS: Baicalein (10mg/kg, intravenous) was administered to conscious Wistar rats 30min after lipopolysaccharide (LPS; 10mg/kg, intravenous) challenge. Six hours after LPS administration, the contractile function of the isolated heart was examined using the Langendorff technique. Cardiac protein expression related to inflammatory responses, superoxide anion production and caspase-3 activity were measured. RESULTS: Post-treatment with baicalein significantly attenuated the LPS-induced hypotension with accompanying tachycardia. The contractile function of isolated heart was significantly preserved 6h after LPS administration, following treatment with baicalein. Furthermore, baicalein induced the expression of heme oxygenase-1 protein and reduced superoxide anion formation in the myocardium of LPS-treated rats. Cardiac levels of inducible nitric oxide synthase, monocyte chemoattractant protein-1, phospho-IκBα and phospho-p65 protein and caspase-3 activity significantly increased 6h after LPS challenge but baicalein significantly attenuated these LPS-induced changes. CONCLUSIONS: Baicalein improves myocardial contractility in LPS-induced sepsis, which may be related to reductions in oxidative stress, myocardial inflammatory responses and apoptosis.