RESUMEN
CONTEXT: Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species. OBJECTIVE: This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats. MATERIALS AND METHODS: Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Pro (70 mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15 mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity. RESULTS: Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes. DISCUSSION AND CONCLUSION: These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.
Asunto(s)
Antioxidantes/uso terapéutico , Cardiomiopatía Dilatada/prevención & control , Cardiotónicos/uso terapéutico , Cardiotoxinas/antagonistas & inhibidores , Doxorrubicina/antagonistas & inhibidores , Extracto de Semillas de Uva/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Proantocianidinas/uso terapéutico , Aconitina/administración & dosificación , Aconitina/antagonistas & inhibidores , Aconitina/toxicidad , Animales , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/antagonistas & inhibidores , Arritmias Cardíacas/etiología , Arritmias Cardíacas/prevención & control , Biomarcadores/sangre , Cardiomiopatía Dilatada/inducido químicamente , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/fisiopatología , Cardiotoxinas/efectos adversos , Doxorrubicina/efectos adversos , Resistencia a Medicamentos/efectos de los fármacos , Corazón/efectos de los fármacos , Corazón/fisiopatología , Masculino , Miocardio/metabolismo , Fitoterapia , Ratas , Ratas Sprague-Dawley , Taquicardia/inducido químicamente , Taquicardia/prevención & control , Agonistas del Canal de Sodio Activado por Voltaje/administración & dosificación , Agonistas del Canal de Sodio Activado por Voltaje/toxicidadRESUMEN
This study was designed to compare the inhibitory effects of thymoquinone (TQ) and curcumin (CMN) on the biological changes associating asthma. TQ appeared to exhibit greater inhibitory effects on the aggregation of inflammatory cells in bronchoalveolar lavage (BAL) fluid and in lung tissues. We also measured the effects of the two agents on serum IgE and the changes in the mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1). Serum IgE was significantly decreased by TQ and CMN with TQ being more potent. Also, TQ showed superior inhibitory effects on iNOS and TGF-ß1. Meanwhile, CMN was more potent in inhibiting mRNA expression of TNF-α. These results suggest that TQ is more potent in inhibiting the inflammatory changes associating asthma. On the other hand, CMN was a less potent inhibitor of all measured parameters, despite its superior inhibitory effect on TNF-α mRNA levels.