RESUMEN

Abstract Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic ß cell function measured by HOMA-ß. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes

Asunto(s)

Animales , Masculino , Ratas , Diabetes Mellitus/patología , Resveratrol/administración & dosificación , Resveratrol/efectos adversos , Células Secretoras de Insulina/clasificación

RESUMEN

OBJECTIVES: It has been shown that dysregulation of miRNAs expression contributes to the pathogenesis and progression of the diabetes and diabetes-related complications. Drosha, DGCR8, Dicer, and Ago-2 are involved in the miRNA maturation. The aim of the present study was to investigate the mRNA expression levels of these genes in the human umbilical vein endothelial cells (HUVECs) under hyperglycemic condition. METHODS: HUVECs were cultured in normo-(5 mM) and hyperglycemic (25 mM) conditions for 24 h. As osmotic control, cells were treated with D-mannitol (25 mM, for 24 h). The mRNA expression levels of Drosha, DGCR8, Dicer and Ago-2 were evaluated using quantitative real-time PCR. RESULTS: The expression level of Drosha, DGCR8, Dicer, and Ago-2 were increased in hyperglycemic HUVECs compared to the control group. CONCLUSION: Our results show that under hyperglycemic condition, expression of genes involved in the miRNA maturation was significantly increased in HUVECs. Upregulation of these genes may have role in diabetic complications through the dysregulation of the miRNA expression.

Asunto(s)

Proteínas Argonautas/genética , ARN Helicasas DEAD-box/genética , Glucosa/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Proteínas de Unión al ARN/genética , Ribonucleasa III/genética , Proteínas Argonautas/metabolismo , Células Cultivadas , ARN Helicasas DEAD-box/metabolismo , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hiperglucemia/genética , Hiperglucemia/metabolismo , Hiperglucemia/patología , Manitol/farmacología , Proteínas de Unión al ARN/metabolismo , Ribonucleasa III/metabolismo

RESUMEN

The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n = 6). Diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1ß (IL-1ß) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.

Asunto(s)

Neuropatías Diabéticas/metabolismo , MicroARNs/metabolismo , FN-kappa B/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal , Estudios de Casos y Controles , Diabetes Mellitus Experimental/inducido químicamente , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/fisiopatología , Prueba de Tolerancia a la Glucosa , Mediadores de Inflamación/metabolismo , Insulina/sangre , Quinasas Asociadas a Receptores de Interleucina-1/genética , Masculino , MicroARNs/genética , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Nervio Ciático/metabolismo , Factor 6 Asociado a Receptor de TNF/genética

RESUMEN

BACKGROUND: High blood glucose levels increase the ratio of phosphorylated to non-phosphorylated connexin-43 amounts, which leads to the decomposition of the hyperphosphorylated connexin-43. This can cause heart arrhythmia in diabetic patients. Considering the effective role of exercise in diabetic patients, and because there are few studies regarding the effect of exercise on phosphorylated connexin-43 protein levels, in the present study the impact of different periods of moderate regular exercise on phosphorylated Connexion-43 levels were examined. METHODS: Sixty (60) male Wistar rats (300 ± 50 g) were randomly divided into six groups (n = 10). A week after induction of diabetes by injection of streptozotocin, one hour treadmill exercise, 5 days a week with 22 (m/min) speeds was undertaken. Left ventricles of hearts were isolated and immediately frozen. Finally, phosphorylated connexin-43 protein levels were measured by ELISA method. RESULTS: The means of blood glucose levels were significantly decreased (P < 0/05) by increasing days of exercise. The means of blood glucose levels were significantly decreased (P < 0/05) by increasing days of exercise. Regular moderate exercise reduced the connexin-43 levels by increasing days of exercise (P < 0.01). CONCLUSION: It is concluded that regular moderate exercise reduces the amount of phosphorylated connexin-43 protein levels in the ventricular myocardium, by reducing blood glucose levels. This can result in partial inhibition of cardiac arrhythmia observed in diabetic patients. This research was done in Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Asunto(s)

Glucemia/metabolismo , Conexina 43/metabolismo , Diabetes Mellitus Experimental/metabolismo , Miocardio/metabolismo , Condicionamiento Físico Animal , Animales , Ventrículos Cardíacos/metabolismo , Miocardio/patología , Fosforilación , Ratas , Ratas Wistar

RESUMEN

BACKGROUND: Based on the key role of hyperglycemia-mediated oxidative stress in the pathogenesis of diabetic cardiomyopathy, increasing antioxidant defense would represent a novel therapeutic approach for management of diabetic cardiomyopathy. This study was designed to seek the effectiveness of chronic treatment with resveratrol, a potent natural antioxidant, on streptozotocin-nicotinamide experimental model of type 2 diabetic hearts. METHODS: Male rats randomized into four groups (n = 12): control, diabetic, control + resveratrol, and diabetic + resveratrol. RESULTS: Four-month oral resveratrol administration to diabetic rats (5 mg/kg/day) alleviated the reduction of cardiac antioxidant enzymes activities (3.88 ± 0.48 vs. 1.49 ± 0.43 U, p < 0.05 for superoxide dismutase, and 2.72 ± 0.26 vs. 1.18 ± 0.19 nmol/min/mL, p < 0.05 for catalase) and the enhancement of cardiac oxidative markers (5.01 ± 0.37 vs. 7.23 ± 0.51 ng, p < 0.05 for 8-isoprostane, 6.03 ± 0.87 vs. 8.49 ± 0.52 µmol, p < 0.05 for nitrite/nitrate, and 0.44 ± 0.03 vs. 0.59 ± 0.04, p < 0.05 for oxidized/reduced glutathione ratio), nuclear factor kappa B activity (0.37 ± 0.09 vs. 0.60 ± 0.11, p < 0.05) and apoptosis rate (0.98 ± 0.28 vs.1.63 ± 0.16, p < 0.05). Moreover, it improved left ventricular developed pressure (72.46 ± 8.16 vs. 52.01 ± 11.32 mm Hg, p < 0.05) and coronary flow (14.08 ± 1.09 vs. 11.75 ± 1.43 mL/min × g, p < 0.05). CONCLUSIONS: These beneficial cardioprotective observations suggest that treatment with resveratrol can potentially delay or attenuate the progression of diabetes-related cardiac complications.

Asunto(s)

Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Estilbenos/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Sprague-Dawley , Resveratrol , Ribonucleótido Reductasas/antagonistas & inhibidores

RESUMEN

The present study was designed to evaluate whether microRNA-146a and its adapter proteins (TRAF6 and IRAK1) are involved in the pathogenesis of diabetes-induced kidney damage. Male Sprague-Dawley rats were divided into control and diabetic groups (n = 6 in each). Diabetes was induced by injection of streptozotocin (55 mg/kg; i.p.) in 12 h fasted rats. Diabetic kidney damage was diagnosed by renal hypertrophy, thickened glomerular basement membrane, widened filtration slits, mesangial expansion, as well as by elevated levels of blood urea and creatinine in diabetic rats 2 months after induction of diabetes. While the expression of NF-κB mRNA and miR-146a were increased in diabetic kidney compared to the sham controls (p < 0.01 for both comparisons), the mRNA levels of IRAK1 and TRAF6 did not statistically reduce. The NF-κB activity and the concentrations of TNF-α, IL-6 and IL-1ß in the kidney of diabetic rats were higher than the kidney of controls (p < 0.05 for TNF-α and NF-κB; p < 0.01 for IL-6 and IL-1ß). Our results indicate that the upregulation of miR-146a was not accompanied by downregulation of inflammatory mediators in diabetic kidney. It is possible that a defect in the miR-146a-mediated negative loop provides a situation for sustained activation of NF-κB and its targets to promote cells toward abnormalities.

Asunto(s)

Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Regulación de la Expresión Génica , Mediadores de Inflamación/metabolismo , MicroARNs/genética , Animales , Biomarcadores , Citocinas/sangre , Citocinas/metabolismo , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Mediadores de Inflamación/sangre , Riñón/metabolismo , Riñón/patología , Riñón/ultraestructura , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Glomérulos Renales/ultraestructura , Masculino , FN-kappa B/metabolismo , Ratas

RESUMEN

This study was designed to investigate the possible effectiveness of chronic resveratrol administration on redox state, inflammatory mediators and apoptosis rate in diabetic rats. Male Wistar rats were divided into four groups (n = 6): normal control, diabetic control, normal rats treated with resveratrol, and diabetic rats treated with resveratrol. Diabetes was induced by injection of streptozotocin (50 mg/kg; i.p.), 15 min after the prescription of nicotinamide (110 mg/kg; i.p.) in 12 h-fasted rats. Four-month oral resveratrol administration (5 mg/kg/day) significantly alleviated hyperglycemia, weight loss, enhancement of oxidative markers (lipid peroxidation index, nitrite/nitrate content and oxidized to reduced glutathione ratio) and superoxide dismutase activity in diabetic rats. Moreover, resveratrol administration to diabetic rats improved the elevated levels of plasma TNFα and IL-6 as well as NF-κB activity of polymorphonuclear cells. On the other hand, four months resveratrol administration decreased the apoptosis rate in the kidney, heart, retina, sciatic nerve and the polymorphonuclear cells of diabetic rats. These beneficial antidiabetic observations suggest that treatment with resveratrol may be considered as a therapeutic approach to reduce diabetic-related complications.

Asunto(s)

Apoptosis/inmunología , Citocinas/inmunología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inmunología , Mediadores de Inflamación/inmunología , Estilbenos/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/patología , Hipoglucemiantes/administración & dosificación , Estudios Longitudinales , Masculino , Niacinamida , Ratas , Ratas Wistar , Resveratrol , Estreptozocina , Resultado del Tratamiento

RESUMEN

No disponible

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Increase in heart metabolism during severe exercise facilitates production of ROS and result in oxidative stress. Due to shortage of information, the effect of chronic strength exercise on oxidative stress and contractile function of the heart was assessed to explore the threshold for oxidative stress in this kind of exercise training. Male Wistar rats (80) were divided into two test groups exercised 1 and 3 months and two control groups without exercise. Strength exercise was carried by wearing a Canvas Jacket with weights and forced rats to lift the weights. Rats were exercised at 70% of maximum lifted weight 6 days/week, four times/day, and 12 repetitions each time. Finally, the hearts of ten rats/group were homogenized and (..) (AU)

Asunto(s)

Animales , Ratas , Ejercicio Físico/fisiología , Estrés Oxidativo/fisiología , Tolerancia al Ejercicio/fisiología , Fenómenos Fisiológicos Cardiovasculares , Prueba de Esfuerzo , Estudios de Casos y Controles

RESUMEN

BACKGROUND: This study was designed to investigate the possible effectiveness of resveratrol (trans-3,5,4'-trihydroxystilbene) administration on oxidative stress, nuclear factor κB (NF-κB) activity and apoptosis rate in streptozotocin-nicotinamide-induced diabetic retinopathy. METHODS: Male Wistar rats were divided into four groups: normal control, diabetic control, normal rats treated with resveratrol, and diabetic rats treated with resveratrol. Diabetes was induced by injection of streptozotocin (50 mg/kg; ip), 15 min after the prescription of nicotinamide (110 mg/kg; ip) in 12 h fasted rats. RESULTS: Four-month oral resveratrol administration (5 mg/kg/day) significantly alleviated hyperglycemia, weight loss, enhancement of oxidative markers (lipid peroxidation index and oxidized to reduced glutathione ratio) and superoxide dismutase activity in both blood and retinas of the diabetic rats. Moreover, resveratrol administration to diabetic rats improved the elevated levels of retinas NF-κB activity and apoptosis rate. On the other hand, four months resveratrol administration prevented from disarrangement and reduction in thickness of retinal layers. CONCLUSION: These beneficial antidiabetic observations suggest that resveratrol may be considered as a therapeutic supplement to prevent from diabetic retinopathy.

Asunto(s)

Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/prevención & control , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estilbenos/farmacología , Administración Oral , Animales , Antioxidantes/administración & dosificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Glutatión/metabolismo , Hemoglobina Glucada/metabolismo , Insulina/sangre , Peroxidación de Lípido/efectos de los fármacos , Masculino , Niacinamida , Oxidación-Reducción , Ratas , Ratas Wistar , Resveratrol , Retina/metabolismo , Retina/patología , Estilbenos/administración & dosificación , Estreptozocina , Superóxido Dismutasa/metabolismo , Factores de Tiempo

RESUMEN

Increase in heart metabolism during severe exercise facilitates production of ROS and result in oxidative stress. Due to shortage of information, the effect of chronic strength exercise on oxidative stress and contractile function of the heart was assessed to explore the threshold for oxidative stress in this kind of exercise training. Male Wistar rats (80) were divided into two test groups exercised 1 and 3 months and two control groups without exercise. Strength exercise was carried by wearing a Canvas Jacket with weights and forced rats to lift the weights. Rats were exercised at 70% of maximum lifted weight 6 days/week, four times/day, and 12 repetitions each time. Finally, the hearts of ten rats/group were homogenized and MDA, SOD, GPX, and catalase (CAT) were determined by ELISA method. In other ten rats/group, left ventricle systolic and end diastolic pressures (LVSP and LVEDP) and contractility indices (LVDP and +dp/dt max) and relaxation velocity (-dp/dt max) were recorded. The coronary outflow was collected. Short- and long-term strength exercise increased heart weight and heart/BW ratio (P < 0.05). In the 3-month exercise group, basal heart rate decreased (P < 0.05). LVEDP did not change but LVDP, +dp/dt max, -dp/dt max, and coronary flow significantly increased in both exercise groups (P < 0.05). None of MDA or SOD, GPX, and CAT significantly changed. The results showed that sub-maximal chronic strength exercise improves heart efficiency without increase in oxidative stress index or decrease in antioxidant defense capacity. These imply that long-time strength exercise up to this intensity is safe for cardiac health.

Asunto(s)

Miocardio/metabolismo , Estrés Oxidativo , Entrenamiento de Fuerza/efectos adversos , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Catalasa/metabolismo , Vasos Coronarios/fisiopatología , Glutatión Peroxidasa/metabolismo , Ventrículos Cardíacos/enzimología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Técnicas In Vitro , Masculino , Malondialdehído/metabolismo , Contracción Miocárdica , Miocardio/enzimología , Miocardio/patología , Tamaño de los Órganos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo

RESUMEN

BACKGROUND: Discovering an effective approach to provide cardioprotection against coronary artery disease has long been sought. We studied the cardioprotective effect of resistance training against ischemia-reperfusion-induced injury. METHODS: Twenty male rats were divided into trained and sedentary groups (n = 10 in each). The rats were exercised in squat-training apparatus (12 repetitions/set, four sets/day and five days/week for 12 weeks). After the last training session, transient regional ischemia of left anterior descending coronary artery (40 min) was followed by 80 min of reperfusion. Coronary flow, left ventricular developed pressure, diastolic pressure and infarct size were measured. RESULTS: After 35 min of ischemia, coronary flow and developed pressure were higher in trained than untrained groups (10.37 ± 0.96 vs 7.54 ± 0.89 mL/min × g, p < 0.01 for coronary flow and 67.74 ± 3.31 vs 52.39 ± 4.28 mm Hg, p < 0.01 for developed pressure) and this difference persisted until 50 min of reperfusion (10.59 ± 0.88 vs 7.71 ± 0.73 mL/ /min × g, p < 0.01 for coronary flow and 58.12 ± 4.07 vs 39.56 ± 3.79 mm Hg, p < 0.01 for developed pressure). Diastolic pressure was significantly lower from 35 min of ischemia (11.51 ± 5.37 vs 24.53 ± 5.44 mm Hg, p < 0.05) through 35 min of reperfusion in trained rather than sedentary rats (30.62 ± 3.19 vs 43 ± 7.11 mm Hg, p < 0.01). Resistance exercise training reduced the infarct size statistically in trained rats as compared with sedentary animals (39.32 ± 4.09 vs 29.36 ± 4.17 percentage of zone at risk, p < 0.05). CONCLUSIONS: These results show that chronic resistance exercise provides cardioprotection against myocardial injuries.

Asunto(s)

Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Daño por Reperfusión Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/terapia , Entrenamiento de Fuerza/métodos , Animales , Circulación Coronaria/fisiología , Modelos Animales de Enfermedad , Corazón/fisiología , Masculino , Actividad Motora/fisiología , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Ratas , Ratas Wistar , Conducta de Reducción del Riesgo , Conducta Sedentaria , Presión Ventricular/fisiología

RESUMEN

This study investigated the onset of age-related changes in the myocardial antioxidant enzymes and apoptosis and the vulnerability of the myocardium to oxidative stress following exercise training. Few studies have investigated the influence of the most prevalent life-prolonging strategy physical exercise, on the age increment alterations in the myocardial antioxidant enzymes and apoptosis at mid age and to determine whether exercise-induced antioxidant defense system could attenuate lipid peroxidation. Thirty six male Wistar rats were randomly assigned to exercise trained (n = 18) and sedentary (n = 18) groups. The rats in the training group went under 12, 24 and 36 weeks of moderate exercise trainings (25 m·min(-1) for 60-min with a 0% slope). Six sedentary controls were killed together with each exercise group at the end of the training programs. Levels of thiobarbituric acid-reactive substances (TBARS) and catalase (CAT) activity in myocardial homogenates were unchanged by training irrespective of the protocol duration. However, an increased content of the TBARS was detected in hearts from both the 24 and 36-week trained and sedentary control rats when compared with their corresponding 12-week groups (p<0.01). The activity of superoxide dismutase (SOD) remained unchanged after the 12-week training period whereas a significant increase was observed in heart homogenates of 24-week trained animals as compared with their sedentary controls (p<0.05). The activity of glutathione peroxidase (GPX) remained unchanged. The rates of apoptosis which was detected by ELISA assays, were significantly modified after 24 and 36-week of training (p<0.05). These results demonstrate that a long-term endurance training (24 weeks) induced increases in SOD activities in rat myocardium and elicited a marked reduction in apoptosis rate. However, a shorter training program (12 weeks) was not effective in increasing heart antioxidant defenses. Key pointsExercise training induces activity of myocardial SOD.Long-term regular moderate-intensity exercise decreases the rate of myocardial apoptosis.Short-term regular moderate-intensity exercises do not change the rate of myocardial anti oxidant capacity and apoptosis.