Jabuticaba [Plinia trunciflora (O. Berg) Kausel] Protects Liver of Diabetic Rats Against Mitochondrial Dysfunction and Oxidative Stress Through the Modulation of SIRT3 Expression.

Complications generated by hyperglycemia present in diabetes mellitus (DM) have been constantly related to oxidative stress and dysfunction in the mitochondrial electron transport chain (ETC). Sirtuin 3 (SIRT3), which is present in mitochondria, is responsible for regulating several proteins involved in metabolic homeostasis and oxidative stress. Studies have suggested alterations in the expression of SIRT3 in DM. The objective of this study was to evaluate the effects of phenolic compounds in jabuticaba (Plinia trunciflora), a berry native to Brazil, on the activity of mitochondrial ETC complexes, SIRT3 protein expression, and oxidative stress parameters in liver of diabetic rats induced by streptozotocin. After type 1 DM induction (streptozotocin 65 mg/kg), diabetic and healthy rats were treated with jabuticaba peel extract (JPE) by gavage (0.5 g/kg of weight) for 30 days. After treatments, those diabetic rats presented impaired activities of complexes I, II, and III of ETC along with an overexpression of SIRT3. In addition, an increase in lipid peroxidation and superoxide dismutase and catalase activities was observed in the diabetic group. The treatment with JPE was able to recover the activity of the mitochondrial complexes and reduce the expression of SIRT3. Furthermore, JPE treatment reduced oxidative damage to lipids and brought the antioxidants enzyme activities to basal levels in diabetic rats. Together, these results demonstrate that JPE can reduce oxidative stress related to DM by restoring mitochondrial complexes activity and regulating SIRT3 expression. Thus, JPE could become an alternative to reduce the development of complications related to DM.

Age-related effects of DHEA on peripheral markers of oxidative stress.

Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10-20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto-oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month-old. In the 13 month-old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione-S-transferase and catalase activities when compared to the other age groups. DHEA produced a marked increase in LPO of 13 month-old group when compared to its control. DHEA exerted this pro-oxidant effects in all ages studied, especially in age 13 month-old. It seems that at 13 month-old there would be an important depletion of some specific anti-oxidant in order to determine such susceptibility to DHEA effects. Since this approach allows a minimally invasive assessment, it would be useful as a routine method in human clinical studies investigating DHEA effects during the ageing process.

The effect of aqueous extract of gross and commercial yerba mate (Ilex paraguariensis) on intra-abdominal and epididymal fat and glucose levels in male Wistar rats.

This study analyzed the plasma lipid profile, glucose levels and fat deposits in male rats treated with aqueous extract of gross yerba mate, commercial yerba mate or water. Yerba mate treatment did not change body weight gain and lipid profile. The consumption of gross yerba mate significantly increased blood glucose (6.6 mmol/L) as compared to the water (4.8 mmol/L) and commercial group (5.2 mmol/L) and decreased epididymal and intra-abdominal deposits (10.1mg/g and 23.7 mg/g of weight) as compared to the water (15.4 mg/g and 36.9 mg/g of weight) and commercial group (12.5mg/g and 28 mg/g of weight). The results suggest that gross yerba mate reduces fat more efficiently but produces a greater increase in blood glucose when compared to commercial yerba mate and water groups.

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor ß(1) (TGF-ß(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-ß(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-ß(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.

Dehydroepiandrosterone improves hepatic antioxidant reserve and stimulates Akt signaling in young and old rats.

This study examined, in the liver of young and old (3- and 24-month-old, respectively) healthy Wistar rats, the in vivo effect of dehydroepiandrosterone (DHEA) (10mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities, hydrogen peroxide concentration, GST and p-Akt/Akt immunocontent ratio were assessed in hepatic tissue. DHEA treatment significantly increased total glutathione content (17%) and GSH (22%) in 3- and 24-month-old treated groups when compared to control groups. The aging factor increased G6PDH (51%) and GPx (22%) activities as well as the hydrogen peroxide concentration (33%), independently of treatment. DHEA treatment increased p-Akt (54%) and p-Akt/Akt ratio (36%) immunocontents in both treated groups. Increased serum levels of alanine aminotransferase (ALT) in aged rats were reduced by DHEA treatment (34%).

Redox imbalance influence in the myocardial Akt activation in aged rats treated with DHEA.

This study examined, in young and old (3 and 24 month-old, respectively) healthy Wistar rats, the in vivo effect of DHEA (10 mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and thioredoxin (Trx) reductase activities, hydrogen peroxide steady-state concentration and Nrf2, GST, Trx-1, Akt and p-Akt expressions were assessed in heart tissue. DHEA treatment significantly increased GST activity in 3 and 24 month-old treated groups. The aging factor diminished hydrogen peroxide concentration and Nrf2 expression, independently of treatment. However, the aging process increased GST, Akt and p-Akt expressions in both 24 month-old groups. The aged group responded differently to DHEA respective to GSSG content, GPx activity and p-Akt concentration. Further studies are needed to form conclusions about the efficacy and safety of DHEA replacement in the elderly, and to better understand DHEA's net effect on oxidative stress parameters and its modulation of signaling cascades.

The effect of long-term DHEA treatment on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of diabetic rats.

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions. This study shows the effects of DHEA on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of control and diabetic rats. Control and diabetic rats were chronically treated with DHEA (10mg/kg) diluted in oil. Plasma concentration of DHEA and glucose, glucose uptake and oxidation, hydrogen peroxide, GLUT4, Akt and thioredoxin (Trx) was measured in the muscle. Results showed that there was a decrease in blood glucose in diabetic rats, probably linked to an increase in the glucose oxidation by the muscle or glucose uptake by some tissues. Despite the increase in the expression of GLUT4 in DHEA-treated rats, the glucose uptake was only higher in the control rats, showing that the glucose transporter may be present but not functional in the diabetic rats. The low expression of Trx due to diabetes became even lower with DHEA treatment. Although the reduction in blood glucose may be favorable, the decrease in Akt and Trx displays an environment conducive to redox imbalance. Thus, further studies are needed to ascertain the effects of DHEA treatment in diabetic rats.

DHEA effects on myocardial Akt signaling modulation and oxidative stress changes in aged rats.

The secretion of DHEA-synthesized mainly in the adrenal cortex-increases in the postnatal aging, peaks in the twenties and decreases with age afterwards. Exogenous DHEA can exert a dual effect depending on dose and on tissue. Akt is a serine/threonine kinase whose activity has been seen as an interventional approach for cardiomyopathic damage resulting from aging changes. In order to evaluate DHEA effects over myocardial Akt protein expression associated to oxidative stress markers during aging, male Wistar rats (3 and 18 months) were assigned into two groups: control or DHEA (10mg/kg, subcutaneously, for 5 weeks). In the aged group, we found increased lipid peroxidation and glutathione-S-transferase activity. DHEA produced an increase in p-Akt protein expression and a decrease in SOD activity in both ages. Akt pathway activation might be related to changes in oxidative stress parameters according to age.

Efeito do extrato aquoso de Ilex Paraguariensis sobre o metabolismo de ratos machos / Effect of aqueous extract of Ilex Paraguariensis on the metabolism of male rats

Introdução: Vários estudos têm apontado Ilex paraguariensis (erva-mate) como coadjuvante no manejo da obesidade. Objetivo: O objetivo do estudo foi avaliar ingestão alimentar, peso corporal, volume da diurese, quantidade de gordura abdominal, triglicérides e colesterol total plasmáticos de ratos Wistar machos tratados com extrato aquoso de Ilex paraguariensis. Métodos: Formaram-se dois grupos de seis animais cada, um controle e outro tratado. O tratado recebia extrato de Ilex paraguariensis e o controle, água para hidratação. Todos receberam ração padrão. Para o preparo do extrato da erva, misturava-se 1 l de água aquecida à 80ºC e 70 g de erva-mate. Em 15 minutos, essa mistura era coada. Após 8 semanas, os animais foram colocados em gaiolas metabólicas para avaliar a ingestão alimentar e hídrica e o volume de diurese e fezes. Nesse período, foi aferido o peso, foram coletadas amostras de sangue para quantificar triglicérides e colesterol e a gordura abdominal foi dissecada após a morte dos animais. Na análise estatística, foi utilizado o teste t de Student para o tratamento de todos os resultados, e P<0,05 foi considerado significativo. Resultados: Ingestão alimentar e hídrica, diurese, fezes e peso dos animais não apresentaram qualquer diferença significativa, assim como os níveis de triglicérides. A quantidade de gordura abdominal, assim como os níveis de colesterol, foram significativamente menor nos animais tratados. Conclusão: O extrato da erva-mate parece ter influência sobre o metabolismo dos lipídios sem interferir no peso corporal nem na ingestão alimentar e hídrica.

Introduction: Some studies have shown Ilex paraguariensis (yerba mate) as an adjuvant in overweigh treatment. Aim: Our aim was to measure food intake, body weight, urine volume, feces, abdominal fat, triglycerides and cholesterol plasmatic in rats treated with aqueous extract of Ilex paraguariensis. Methods: We used two groups of six animals each, a control group and a treated group. Animals in the treated group received Ilex paraguariensis in aqueous extract and the controls were given only water for hydration. Both groups received standard food. To prepare the Ilex paraguariensis extract, we mixed 1 L of hot water (80ºC) and 70 g of yerba mate. After 15 minutes, we strained the mixture. After eight weeks, the animals were allocated in metabolic cages to measure food intake, hydration, urine volume and feces. During this time, we also measured body weight, collected blood samples for triglycerides and cholesterol analyses. Abdominal fat was dissected after the animals died. For statistical analyses, we used t student for all data. P<0.05 was considered significant. Results: No significant difference was observed in food intake, hydration, urine volume, feces and body weight, as well as triglycerides. The amount of abdominal fat and plasmatic cholesterol was significantly lower in treated animals. Conclusions: The aqueous extract of Ilex paraguariensis seems to effect in the metabolism of the lipids without modifying body weight, food intake or hydration.