RESUMEN
Oxidative stress is a major cause of cardiovascular tissue fibrosis. We evaluated the effects of daily doses of soy isoflavones, genistein and daidzein on cardiovascular tissue fibrosis in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats and Long-Evans Tokushima Otsuka (LETO) non-diabetic rats as a severe or mild oxidative stress model, respectively. Glucose and lipid metabolisms did not improve with genistein or daidzein treatment. However, genistein decreased hydroxyproline concentrations in the heart. Hydroxyproline reductions as a result of genistein were mildly stronger than those of daidzein. Thus, genistein significantly suppressed the progression of myocardial fibrosis in LETO rats despite the insignificant changes in OLETF rats. Although a daily dosage of isoflavone was not sufficient to prevent tissue fibrosis under marked oxidative stress in the early stage of diabetes, isoflavones might promise significant clinical benefits by reducing oxidative stress in the heart during aging.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Isoflavonas/administración & dosificación , Fitoestrógenos/administración & dosificación , Alimentos de Soja , Análisis de Varianza , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patología , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/patología , Sistema Cardiovascular/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Fibrosis , Frecuencia Cardíaca/efectos de los fármacos , Hidroxiprolina/efectos de los fármacos , Hidroxiprolina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Miocardio/metabolismo , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: D-allose, an all-cis aldo-hexose, is non-caloric and possesses antioxidant properties. We investigated the effects of oral D-allose supplementation on the development of high blood pressure and the oxidative status in two genetically hypertensive animal models: Dahl salt-sensitive hypertensive (DS) rats and spontaneously hypertensive rats. METHODS AND RESULTS: The systolic blood pressure of DS rats fed a 4% salt diet for 4 weeks significantly increased from 122+/-8 to 161+/-5 mmHg as compared with DS rats fed a normal salt diet (138+/-5 mmHg at 4 weeks), whereas concordant supplementation of D-allose, but not D-glucose, with a dose of 2 g/kg daily to salt-loaded DS rats suppressed the development of high blood pressure (135+/-7 mmHg at 4 weeks), accompanied with decreases in superoxide production in the aorta that was determined by the lucigenin chemiluminescence and dihydroethidium staining. The increases of urinary protein secretion of salt-loaded DS rats were prevented by D-allose supplementation (DS rats fed 0.5% salt, 18.2+/-6.3 mg/day; DS rats fed 4% salt alone, 81.8+/-16.5 mg/day; DS rats fed 4% salt+D-allose, 31.3+/-11.8 mg/day; DS rats fed 4% salt+D-glucose, 85.3+/-20.5 mg/day). On the other hand, D-allose supplementation in spontaneously hypertensive rats had no significant effect on the blood pressure or the aortic superoxide production during the early developing stage of hypertension. CONCLUSIONS: These results underscore the role of enhanced oxidative stress in the pathogenesis of high blood pressure development in DS rats, and suggest the possibility of D-allose supplementation for prevention of salt-sensitive hypertension.