Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats

Oxidative stress plays the central role in the pathogenesis and progression of diabetic complications. The present study aims to investigate the beneficial effect of oral administration of flavone baicalein in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats by measuring oxidative stress markers, antioxidant enzyme activities and expression analysis of antioxidant genes. Experimental diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (55 mg /kg b.wt), 15 min after the i.p. administration of NA. At the end of the experimental period, thiobarbituric acid reactive substances (TBARS), activities of antioxidant enzymes and expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) were measured in diabetic rats along with serum biochemical parameters namely total cholesterol (TC), total triglyceride (TG), aspartate transaminase (AST) alanine transaminase (ALT) and glycosylated hemoglobin (HbA1c). Oral administration of baicalein (40 mg/kg b.wt/day) demonstrated a significant ameliorative effect on all studied biochemical and oxidative stress parameters. Biochemical findings were corroborated by qPCR expression analysis which showed significant upregulation of antioxidant genes in diabetic rats. These results suggest that baicalein supplementation may reduce diabetes and its complications by suppressing oxidative stress and enhancing gene expression and antioxidant enzyme activities in diabetic rats.

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

ABSTRACT Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group

Low-level laser therapy associated to a resistance training protocol on bone tissue in diabetic rats

ABSTRACT Objective The present study aimed to evaluate the in vivo response of a resistance training and low-level laser therapy (LLLT) on tibias and femurs of rats with diabetes mellitus (DM). Materials and methods Forty male Wistar rats were randomly distributed into four experimental groups: control group (CG), diabetic group (DG), diabetic trained group (TG) and diabetic trained and laser irradiated group (TLG). DM was induced by streptozotocin (STZ) and after two weeks laser and resistance training started, performed for 24 sessions, during eight weeks. At the end of the experiment, animals were euthanized and tibias and femurs were removed for analysis. Histological, histomorphometrical, immunohistochemistry and mechanical analyses were performed. Results Trained groups, with or without laser irradiation, showed increased cortical area, bone density and biomechanical properties. The immunohistochemical analysis revealed that TG and TLG demonstrated an increased RUNX2 expression. RANK-L immunoexpression was similar for all experimental groups. Conclusion In conclusion, it can be suggested that the resistance exercise program stimulated bone metabolism, culminating in increased cortical tibial area, bone mineral content, bone mineral density and biomechanical properties. Furthermore, the association of physical exercises and LLLT produced higher values for bone mineral content and stiffness. Consequently, these data highlight the potential of physical exercise in the management of bone loss due to DM and the possible extra osteogenic stimulus offered by lasertherapy. Further long-term studies should be carried out to provide additional information.

Green banana pasta diet prevents oxidative damage in liver and kidney and improves biochemical parameters in type 1 diabetic rats

ABSTRACT Objective In this study, the effects of a green banana pasta diet on the oxidative damage from type 1 diabetes mellitus (DM) were investigated. Materials and methods Formulations containing 25 (F25), 50 (F50), and 75% (F75) of green banana pasta were prepared and included in a 12-week diet of Wistar rats with alloxan-induced type 1 DM. The effects of these formulations in preventing oxidative damage in kidneys and liver homogenates of rats were evaluated using the TBARS assay (lipid peroxidation in liver) and the DNPH assay (protein oxidation in liver and kidneys). Furthermore, the effects of the formulations on the fasting glycemia, fructosamine levels, renal function (creatinine), liver function (enzymes aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and lipid profile (total cholesterol and fractions) in the serum of rats were evaluated in addition to the evaluation of the centesimal composition and microbiological analysis of the produced green banana pasta. Results An F75 diet prevented hyperglycemia in diabetic rats (p < 0.05) compared to the diabetic rats fed a standard diet (commercial feed). Notably, the protein oxidation in both the liver and kidneys were prevented in diabetic rats on the F50 or F75 diets compared to the control group, whereas the lipid peroxidation was only prevented in the liver (p < 0.05). Moreover, all formulations prevented an increase in the amount of triglycerides in the serum of the rats. The F25 and F50 diet prevented the increase of cholesterol, and the F75-based diet of ALT and fructosamine (p < 0.05) supported the anti-hyperglycemic effects and the protection against oxidative damage. Conclusion The green banana pasta (F75) diet showed great potential for preventing complications associated with diabetes.

The efficacy of SPA0355 in protecting beta cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes

Cytokines activate several inflammatory signals that mediate beta-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting beta cells from various insults. The effects of SPA0355 on beta-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor kappaB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic beta cells in type 1 diabetes.

Efecto de la administración de espironolactona sobre la pérdida de podocitos y la progresión de la nefropatía diabética experimental / Effects of spironolactone administration on the podocytes loss and progression of experimental diabetic nephropathy

Objetivos. Evaluar el efecto de espironolactona (SPL) sobre la pérdida de los podocitos durante la progresión de la nefropatía diabética (ND) experimental. Materiales y métodos. Aleatoriamente un grupo de ratas macho Holtzman recibieron estreptozotocina (grupo diabético) o citrato buffer (grupo control). Las ratas diabéticas fueron tratadas con SPL (50 mg/kg/día). El área glomerular y la celularidad fueron evaluadas por métodos histomorfométricos. La lesión y pérdida de podocitos fue evaluada por la expresión de desmina y Wt-1, respectivamente. La expresión génica del TGF-β1 se evaluó mediante RT-PCR. Resultados. Los niveles de glucosa, el área glomerular, la expansión mesangial y el contenido de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de SPL previno estos cambios sin modificar los niveles de glucosa. La inmunotinción para Wt-1 se redujo significativamente, mientras que la inmunotinción para desmina se incrementó drásticamente en las ratas diabéticas. El tratamiento con SPL previno el incremento de expresión de desmina y la pérdida de expresión de Wt-1. Asimismo, la administración de SPL previno el incremento de la expresión del mRNA del TGF-β1 en las ratas diabéticas. Conclusiones. El tratamiento con SPL, a través de efectos glucosa independientes, atenúa la perdida de podocitos y la progresión de los cambios morfológicos de la ND. Los presentes resultados sugieren que estos efectos son mediados, al menos en parte, por la inhibición de la la expresión del mRNA del TGF-β1.

Objectives. Evaluate the effect of spironolactone (SPL) on the loss of podocytes during the progression of experimental diabetic nephropathy (DN). Materials and methods. A group of male Holtzman rats randomly received streptozotocin (diabetic group) or a buffer citrate (control group). Diabetic rats were treated with SPL (50 mg/kg/day). The glomerular area and the cellularity were evaluated by histomorphometric methods. The injury and loss of podocytes was assessed by desmin expression and Wt-1, respectively. The gene expression of TGF-β1 was assessed by RT-PCR. Results. Glucose levels, the glomerular area, the mesangial expansion and collagen content increased significantly in diabetic rats. The administration of SPL prevented these changes without changing glucose levels. Immunostain for Wt-1 decreased significantly while immunostain for desmin increased dramatically in diabetic rats. Treatment with SPL prevented the increase of desmin expression and the loss of Wt-1 expression. Furthermore, the administration of SPL prevented the increase of TGF-β1 mRNA expression in diabetic rats. Conclusions. Treatment with SPL, through independent glucose effects, reduces the loss of podocytes and the progression of DN morphological changes. These results suggest that these effects are mediated, at least in part, by the inhibition of TGF-β1 mRNA expression.

Spirulina, exercício e controle da glicemia em ratos diabéticos / Spirulina, exercise and serum glucose control in diabetic rats

OBJETIVO: O objetivo do presente estudo foi analisar o efeito da Spirulina e/ou do treinamento físico na homeostase glicêmica de ratos diabéticos. MATERIAIS E MÉTODOS: Ratos Wistar diabéticos aloxânicos foram separados em quatro grupos: diabético controle (DC); diabético Spirulina (DS); diabético exercício (DE); diabético Spirulina exercício (DSE). RESULTADOS: Não foram observadas diferenças significativas entre os grupos para: peso corporal, ingestão alimentar, tolerância à glicose, tolerância à insulina, concentrações de lactato sanguíneo durante teste de esforço. Para as concentrações de insulina, o grupo DS apresentou valor significativamente menor quando comparado ao grupo DC (pâncreas) e DE e DES (soro). CONCLUSÃO: Os protocolos de exercício e de suplementação com Spirulina utilizados no presente estudo não foram suficientes para promover melhora na homeostase glicêmica de ratos diabéticos.

OBJECTIVE: The objective of this study was to analyze the effect of Spirulina and/or exercise training in the control of serum glucose homeostasis in diabetic rats. MATERIALS AND METHODS: Young Wistar rats were induced to diabetes by intravenous alloxan administration and separated into four groups: diabetic control (DC), diabetic Spirulina (DS), diabetic exercise (DE) and diabetic exercise Spirulina (DES). RESULTS: There were no differences between groups with respect to: body weight, food intake, glucose tolerance, insulin tolerance and blood lactate concentrations during a swimming effort test. DS group showed lower insulin concentrations when compared with DC (pancreas) and DE and DES (serum). CONCLUSION: The protocols of exercise and supplementation with Spirulina used in the present study were not able to improve serum glucose homeostasis in diabetic rats.

Dietary restriction prevents diabetogenic effect of streptozotocin in mice.

The beneficial role of dietary restriction (DR) was studied in streptozotocin (STZ)-induced diabetes in mice. The DR mice exhibited the lower blood glucose (mg/dl) level as compared to ad libitum (AL) fed ones. After 3 months’ DR, STZ treatment to both AL and DR mice showed significant (p<0.001) elevation of the blood glucose level in AL-fed mice, while a lower level of glucose was maintained in DR-fed mice. The ability of maintaining a low blood glucose level in STZ-treated DR mice indicated that STZ might have been ineffective from its action on beta cells of pancreas by long-term DR. Thus, these findings suggested that DR may be an important tool for preventing the diabetic conditions. However, further studies are required to know the mechanism(s) of DR protection against diabetogenic action of STZ in experimental animals.

Analysis of myenteric neurons of the cecum of diabetic rats after supplementation with ascorbic acid / Análisis de neuronas mientéricas del ciego de ratas diabéticas después de suplementación con ácido ascórbico

The objective of this work was to investigate the neuroprotective action of the ascorbic acid over the myenteric neurons in the cecum of Wistar rats, four months after induction of the diabetes mellitus experimental with streptozotocin. Three groups with five rats each were used: C- controls, D- diabetic, DA- diabetic treated with ascorbic acid. For evidentiation of the myenteric neurons was carried out to Giemsa's technique. Were evaluated the areas of cell bodies of 500 neurons in each group studied. The quantitative analysis was carried out in an area of 16.6 mm2 in each cecum studied. In the animals diabetic observed elevation of the glycemia and glycated hemoglobin. The supplementation with ascorbic acid was effective under the myenteric neurons of the cecum of diabetics rays, since was presented the effect neuroprotective and neurotrofic.

El objetivo de este trabajo fue verificar el efecto neuroprotector del ácido ascórbico sobre las neuronas mientéricas en el ciego de Rattus Wistar, cuatro meses después de la inducción de diabetes mellitus experimental con estreptozotocina. Utilizamos tres grupos de animales: C- control, D- diabético, DA- diabético tratado con ácido ascórbico. Para la observación de las neuronas mientéricas fue llevado a cabo la técnica de Giemsa. Fueron evaluadas las áreas del soma de 500 neuronas, en cada grupo estudiado. El análisis cuantitativo fue llevado a cabo, en cada ciego, en un área de 16,6 mm². En los animales diabéticos, se observó la elevación de la glicemia y de la hemoglobina glicosilada. La suplementación con ácido ascórbico fue efectiva en las neuronas mientéricas del ciego de animales diabéticos, ya que se produjeron los efectos neuroprotetor y neurotrófico.

The protective effect of Amomum xanthoides extract against alloxan-induced diabetes through the suppression of NFkappaB activation

This study was undertaken to investigate the preventive mechanism of Amomum xanthoides extract against the development of alloxan-induced diabetics of mice. Pretreatment of mice with A. xanthoides extract via intraperitoneum prevented alloxan-induced hyperglycemia and hypoinsulinemia in a dose dependent manner. Histological examination of pancreatic tissue from A. xanthoides extract treated mice showed that the islet cells remain unaffected by alloxan treatment. NFkappaB activation in the pancreas 30 min after alloxan injection (60 mg/kg, iv), as assessed by an electrophoretic mobility shift assay, was not detected in the mice pretreated with A. xanthoides extract. These results suggest that NFkappaB activation may be one of the critical determinant in the progression of the disease. Considering the preventive effect of A. xanthoides extract from alloxan-induced diabetics development, these results may provide the possible therapeutic value of A. xanthoides extract for the prevention of diabetes mellitus progression.

Treinamento aeróbio e prevençäo da diabetes induzida por aloxana em ratos / Aerobic training and prevention of diabetes induced for alloxan in rats

Este trabalho teve como objetivo verificar se o treinamento aeróbio prévio pode prevenir a instalaçäo da diabetes induzida pela aloxana em ratos. Foram utilizados ratos machos wistar (30 dias) separados inicialmente em dois grupos: Treinadas (T = exercício de nataçäo 1h/dia, com sobrecarga de 5 porcento do peso corporal p.c.); Sedentários (S=sem treinamento físico). Após 60 dias foram compostos três novos grupos: T-ALO eS-ALO, ambos injetados i.v. com aloxana (30 mg/kg p.c), S-CIT, que receberam veículo (tampäo citrato). Incidência de diabetes (glicemia > 17,75nM); insulina, proteínas totais e ácidos graxos livres (AGL) séricos; proteinas musculares, insulina pancreática, tecido adiposo epididimal e as áreas sob as curvas de glicose (AG) e insulina (AI) durante Teste de Tolerância à Glicose oral (GTTo), näo diferiram entre os grupos T-ALO e S-ALO. Glicose sérica de T-ALO foi superior à S-CIT, enquanto que o glicogênio muscular de T-ALO foisuperior à S-CIT. A taxa de remoçäo de glicose (Kitt), durante Teste de Tolerância à Insulina (ITTsc) foi superior (80 porcento) à S-ALO. As adaptaçöes, ao nível muscular proporcionadas pelo treinamento físico prévio exerceram algum efeito protetor contra a açäo diabetogênica da alxona, mas näo suficientes para prevenir a instalaçäo do quadro diabético

Effect of streptozotocin induced diabetes and administration of insulin on some blood clotting parameters and platelet count in male albino rats

The prothrombin time, activated partial thromboplastin time, fibrinogen concentration and platelet count were determined in diabetic and insulin treated diabetic mature male albino rats. The values of prothrombin and activated partial thromboplastin time showed significant [p <0.01] decrease in the diabetic and semidiabetic rats at 10 and 20 days following treatment, fibrinogen concentration increased in diabetic rats, 10 and 20 days post-insulin administration and in the semidiabetic rats after 20 days. Platelet count increased significantly in the diabetic rats treated with 40 U insulin daily after 20 days although the clotting parameters were not affected. The results presented are indicative of coagulation activation in diabetic rats and the periodic administration of insulin will reverse the adverse effects of diabetes

The Effect of Pertussis Vaccine and Cyclosporin on Streptozotocin Induced Diabetic Rats

The injection of streptozotocin(stz) at a high dose (60 mg/kg) into young male rats produces direct beta cell destruction and leads to insulin dependent diabetes (IDD). In contrast the injection of multiple smal doses of stz (40 mg/Kg/d for 5 days) produce IDD, which resembles type l diabetes in man. The provocative effects of the pertussis vaccine (PV) and cyclosporin(CA) against the development of IDD induced by stz were studied. When PV in a dose of 3.75 X 10(10) microorganism was administered to single or multiple stz treated rats, hyperglycemia still developed and persisted during the experiment. No difference was noted in blood glucose levels, but plasma insulin levels were higher in PV treated rats. When CA (10 mg/kg) was administered daily to single or multiple stz treated rats, hyperglycemia seemed to be lower, but this was not statistically significant, however, plasma insulin levels were higher in CA treated rats. The results of this experiment suggest that PV and CA provide some protection to the beta cells of the pancreas.

Controle do diabetes por meio do transplante de ilhotas de Langerhans, preparadas sem o emprego da digestäo enzimática: estudo experimental no rato / Control of diabetes by transplantation of islands of Langerhans prepared without the use of enzymatic digestion: experimental study in rats

A eficácia do transplante de ilhotas de Langerhans, obtidas sem o emprego da digestäo pela colagenase e separaçäo pelo gradiente de Ficoll, foi estudada no tratamento da diabete aloxânica em 30 ratos distribuídos em três grupos experimentais: GI - Controle diabético; GII - Transplante Alogênico e GIII - Transplante isogênico. A análise dos resultados permitiu concluir que: a) O transplante corrigiu a diabetes em 45% dos animais estudados e melhorou o quadro clínico-laboratorial em 70% dos ratos diabéticos tratados; b) O número de ilhotas obtidas por doador é elevadíssimo, entretanto, apenas 5% das mesmas säo viáveis, o que torna a proporçäo de doadores para cada receptor semelhante a observada com o emprego da digestäo enzimática; c) o método mecânico é mais simples, barato e proporciona um tempo de isquemia menor do que quando se emprega a colagenase; d) o retorno da hiperglicemia no transplante alogênico deve-se ao processo de rejeiçäo, pois neste grupo as ilhotas transplantadas eram incompatíveis sob o ponto de vista imunológico