RESUMO
The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Spragueâ»Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.
Assuntos
Frutas/química , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo , Panax/química , Fenóis/uso terapêutico , Remodelação Ventricular , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Peso Corporal/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Citocinas/biossíntese , Diástole , Testes de Função Cardíaca , Imunofenotipagem , Inflamação/patologia , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Fenóis/farmacologia , Ratos Sprague-Dawley , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Patients with diabetes mellitus have an increased risk of mortality due to cardiovascular complications. Supplementation with specific sulphur-containing amino acids is rapidly emerging as a possible therapeutic adjuvant for diabetes and associated cardiovascular complications. OBSERVATIONS: It is well-known that oxidative stress plays an important role in the pathogenesis of diabetes-induced cardiovascular disease, which is invariably associated with abnormal blood lipid profile, insulin resistance and other symptoms of metabolic syndrome. Cysteine and taurine are among the most common sulphur-containing amino acids and their cellular levels decline during diabetes that may contribute to the development of the cardiomyopathy. Although sulphur-containing agents exert multiple actions on cellular and subcellular functions in the heart, they also exhibit antioxidant properties and thus may exert beneficial effects in different pathophysiological conditions. CONCLUSION: It is concluded that reduction of oxidative stress by cysteine and taurine may serve as an important mechanism for the attenuation of diabetes-induced subcellular and functional abnormalities in the heart.
Assuntos
Aminoácidos/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Enxofre/farmacologia , Animais , Diabetes Mellitus/fisiopatologia , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/fisiopatologia , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP3/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP3/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP3/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Chá , Vanadatos/farmacologia , Animais , Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Ácidos Fosfatídicos/farmacologia , Ratos , Ratos Sprague-Dawley , Vanadatos/administração & dosagemRESUMO
In an earlier study, we showed that dietary conjugated linoleic acid (CLA) isomers can exert differential effects on heart function in male and female rats, but the underlying mechanisms for these actions are not known. Cardiomyocyte Ca2+ cycling is a key event in normal cardiac contractile function and defects in Ca2+ cycling are associated with cardiac dysfunction and heart disease. We therefore hypothesized that abnormalities in the sarcolemmal (SL) and sarcoplasmic reticulum (SR)-mediated regulation of intracellular Ca2+ contribute to altered cardiac contractile function of male and female rats owing to dietary CLA isomers. Healthy male and female Sprague-Dawley rats were fed different CLA isomers, (cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as triglyceride or fatty acids) from 4 to 20 weeks of age. We determined the mRNA levels of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 2a, ryanodine receptor, phospholamban, calsequestrin, Na+-Ca2+-exchanger (NCX), and L-type Ca2+ channel in the left ventricle (LV) by RT-PCR. The SR function was assessed by measurement of Ca2+-uptake and -release. Significant gender differences were seen in the LV NCX, L-type Ca2+ channel, and ryanodine receptor mRNA expression levels in control male and female rats. Dietary CLA isomers in the various forms induced changes in the mRNA levels of SERCA 2a, NCX, and L-type Ca2+ channel in the LV of both male and female hearts. Whereas protein contents of the Ca2+ cycling proteins were altered, changes in SR Ca2+-uptake and -release were also detected in both male and female rats in response to dietary CLA. The results of this study demonstrate that long-term dietary supplementation can modulate cardiac gene expression and SR function in a gender-related manner and may, in part, contribute to altered cardiac contractility.