Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Antioxidant, Antidiabetic and Lipid Profiling of Spermadicyton Suaveolens in Streptozotocin (STZ) Induced Diabetic Rats

ABSTRACT Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen's roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia

Study of antidiabetic activity of two novel Schiff base derived dibromo and dichloro substituted compounds in streptozotocin-nicotinamide-induced diabetic rats: pilot study

Abstract Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat's liver and can be responsible for causing much healthier structure and notable morphology improvement.

Renal protective effect of ellipticine against streptozotocin induced diabetic nephropathy in rats via suppression of oxidative stress and inflammatory mediator

Purpose: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. Methods: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Results: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Conclusions: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.

Effects of Astragalus membranaceus, Peumus boldus and Curcuma longa extracts in diabetic rats / Efeitos de extratos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida

Objectives: the aim of this study was to evaluate the effects of the association of dry extracts of Astragalus membranaceus, Peumus boldus and Curcuma longa in rats with induced diabetes. Methods: After the induction of type 2 diabetes by intraperitoneal streptozotocin, male Wistar rats were randomly assigned to groups (n=6) and treated for 20 days. The extracts were suspended in water and administered through orogastric gavage once daily as described: Group I: healthy control (saline); group II: received Astragalus membranaceus, Peumus boldus and Curcuma longa (400 mg/kg/day of each dry extract); group III: received Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/day of each dry extract) and glibenclamide (15 mg/kg/day). Fasting glucose, glucose tolerance, alanine aminotransferase, aspartate aminotransferase and fructosamine were evaluated. Results: Fasting blood glucose and glucose tolerance for groups II and III were influenced by treatments (p<0.05). The extracts did not significantly influence the efficacy of glibenclamide. Conclusion: The results found in this study allow us to consider that it is not possible to conclude that the compounds evaluated are not effective in DM in rats, due to variables such as total treatment period, doses, size of pancreatic injury caused by streptozotocin, and diet profile may have influenced the results. The studied compounds have potential for application in diabetes and further studies should be carried out to adjust the treatment.

Objetivos: avaliar os efeitos da associação de extratos secos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida. Métodos: Após a indução de diabetes tipo 2 (DM) por estreptozotocina intraperitoneal, ratos Wistar machos foram distribuídos aleatoriamente em grupos (n=6) e tratados por 20 dias. Os extratos foram suspensos em água e administrados por gavagem orogástrica uma vez ao dia conforme descrito: Grupo I: controle saudável (solução salina); grupo II: recebeu Astragalus membranaceus, Peumus boldus e Curcuma longa (400 mg/kg/dia de cada extrato seco); grupo III: receberam Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/dia de cada extrato seco) e glibenclamida (15 mg/kg/dia). A glicemia de jejum, tolerância à glicose, alanina aminotransferase, aspartato aminotransferase e frutosamina foram avaliados. Resultados: A glicemia de jejum e a tolerância à glicose para os grupos II e III foram influenciadas pelos tratamentos (p<0,05). Os extratos não influenciaram significativamente na eficácia da glibenclamida. Conclusão: Os resultados encontrados neste estudo permitem considerar que não é possível concluir que os compostos avaliados não são eficazes no DM em ratos, devido às variáveis como tempo total de tratamento, doses e tamanho da lesão pancreática causada por estreptozotocina, além do perfil da dieta, que podem ter influenciado os resultados. Os compostos estudados têm potencial para aplicação em diabetes e mais estudos devem ser realizados para adequar o tratamento.

Efectos de la inyección neonatal de estreptozotocina sobre indicadores bioquímicos y de estrés oxidativo en ratas / Effects of neonatal injection of streptozotocin on biochemical indicators and oxidative stress in rats

Introducción: Debido a sus propiedades químicas, la estreptozotocina es uno de los agentes diabetogénicos más utilizados para generar modelos biológicos de diabetes, por lo que es necesario estudiar cuáles son sus efectos en el organismo del animal de laboratorio. Objetivo: Evaluar, en un periodo de 90 días, los efectos de la inyección neonatal de estreptozotocina en ratas Wistar sobre indicadores bioquímicos y de estrés oxidativo en hígado y riñón. Métodos: La diabetes fue inducida neonatalmente por 100 mg de estreptozotocina en ratas Wistar. Se realizaron determinaciones de glucemia, insulina e indicadores de estrés oxidativos en hígado y riñón en cinco animales por grupo a los días 5, 10, 20, 30, 60, 90 de nacidos. Resultados: En todas las intervenciones, la glucemia e insulina mostraron diferencias significativas en el grupo-STZ respecto al control. El valor máximo de hiperglucemia se observó al quinto día. La concentración de nitratos y nitritos en hígado fue mayor que en riñón. En comparación con el grupo control, en el tejido hepático del grupo-STZ la concentración de nitratos y nitritos resultó significativamente superior los días 10-20. En todas las intervenciones se detectó consumo de glutatión reducido en ambos órganos. En el hígado de las ratas STZ no se demostró daño a lípidos ni proteínas; sin embargo, en riñón se detectó daño significativo en ambas biomoléculas al quinto día. Conclusiones: Tanto la citotoxicidad de la estreptozotocina neonatal como las concentraciones de glucosa e insulina inducidas repercutieron negativamente sobre los indicadores de estrés oxidativo estudiados en tejido hepático y renal(AU)

Introduction: Streptozotocin is currently one of the most used diabetogenic agents to generate biological models of diabetes due to its chemical properties, so it is necessary to study the consequences of STZ for the organism of the laboratory animal. Objective: To evaluate in a period of 90 days the effects of neonatal injection of streptozotocin in Wistar rats on biochemical indicators and oxidative stress in liver and kidney. Methods: Diabetes was induced neonatally by 100 mg of streptozotocin in Wistar rats. Blood glucose, insulin and oxidative stress indicators in liver and kidney were determined in 5 animals per group at days 5, 10, 20, 30, 60, 90 of birth. Results: Blood glucose and insulin showed significant differences in the STZ-group respect to the control group in all interventions. The maximum value of hyperglycemia was observed on day-5. The concentration of nitrates and nitrites in liver was higher than in kidney. In liver tissue of the STZ-group, this indicator was significantly higher on days 10-20 compared to the control. In all interventions, reduced glutathione consumption was demonstrated in the STZ-group compared to control in both organs. In the liver of STZ rats no lipid or protein damage was demonstrated. However, in the kidney, significant damage in both biomolecules was detected in the STZ-group on day-5. Conclusions: Neonatal streptozotocin cytotoxicity as well as induced glucose and insulin concentrations had a negative impact on oxidative stress indicators studied in liver and kidney tissue(AU)

Investigation of the protective and therapeutic effects of ß-aminoisobutyric acid (BAIBA) and Thymoquinone in the diabetic nephropathy / Investigación de los efectos protectores y terapéuticos del ácido ß-aminoisobutírico (BAIBA) y la timoquinona en la nefropatía diabética

In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and ß-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney weight, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-α) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.

En este estudio, contra la nefropatía diapética (ND) inducida por estreptozotocina (STZ); tiene como objetivo investigar el uso de timoquinona (TQ) y ácido ß-aminoisobutírico (BAIBA) y comparar los efectos de estos agentes. Con la selección aleatoria de 35 ratas macho, se constituyeron cinco grupos (siete ratas en cada grupo) como sigue: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. En el grupo STZ; el peso corporal, los niveles de glutatión (GSH) y de insulina disminuyeron, el peso relativo de los riñones, el malondialdehído (MDA), la glucosa, el nitrógeno ureico en sangre (BUN) y los niveles de creatinina (Cr) aumentaron. Además, en tejido renal; se detectaron cambios histopatológicos (como engrosamiento de las membranas basales capsular, glomerular y tubular, aumento de la cantidad de matriz mesangial, aumento de la vacuolización citoplasmática en algunas de las células epiteliales tubulares, aumento de la expresión del factor de necrosis tumoral alfa (TNF-α) e infiltraciones de células inflamatorias en tejido intersticial). Se observó que estos cambios que ocurren después de la diabetes mellitus (DM) se revirtieron significativamente en los grupos TQ, BAIBA y TQ + BAIBA.

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.

Hypolipidemic, hipoglycemiant and antioxidant effects of Myrcia splendens (Sw) DC in an animal type 2 diabetes model induced by streptozotocin / Efectos hipolipemiante, hipoglucemiante y antioxidante de Myrcia splendens (Sw) DC en un modelo animal de diabetes tipo 2 inducido por estreptozotocina

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.

Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.

Combination of cafeteria diet with intraperitoneally streptozotocin in rats. A type-2 diabetes model

ABSTRACT Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.

Effect on hyperglycemia and pancreas cells of chaya aqueous extracts from two different regions in streptozotocin-induced diabetes rats

Cnidoscolus chayamansa is a native plant of the Mayan region, which is also cultivated in other places like northern Mexico, Tunisia and India. Many properties are attributed to Mayan Chaya, such as aid in the control of glycemia in diabetics. Thus this study aimed to evaluate the hypoglycemic effects of chaya aqueous extracts in a model of streptozotisin-induced diabetic Wistar rats. Chaya aqueous extracts were collected from plants cultivated in Quinta Roo (Mayan region) and Durango (northern Mexico), and in this study we compare their effect with metformin (as a control). Additionally, we compared the extracts mass profiles from both regions by high-resolution liquid chromatography coupled to a triple quadrupole tandem mass detector (HPLC-MS/MS QQQ). Finally, a study of the pancreatic tissue was carried out to evaluate the effects of the extracts on the Langerhans islets. Both extracts showed a good hypoglycemic effect after two weeks of treatment, and the Langerhans islets showed a partial recovery due to the effect of the treatment. Although the plants were cultivated at a distance of 2,350 km and under different weather, the compounds found in both did not show significant differences.

The neurogenic effects of rosmarinic acid in a mouse model of type 2 diabetes mellitus

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer's disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.

Evaluation of antihyperglycemic potential of homeopathic medicines Insulinum, Pancreatinum and Uranium nitricum in Streptozotocin Induced diabetic rats

IntroductionDiabetes Mellitusis an emerging endocrine and metabolic disorder which has affected millions of people globally. Homeopathic system of medicine uses ultra-molecular doses for treatment of Diabetes Mellitus. Homeopathic medicines are prepared from plant, mineral, sarcodes,nosodes and animal parts. Insulinum 6 CH, Pancreatinum 6CH and Uranium nitricum 6 CHareused in homeopathy for treatment of Diabetes Mellitus. However,no preclinical studies have been investigated for the anti-diabetic effect and its safety.MethodsHomeopathic medicines Insulinum 6CH, Pancreatinum 6CHandUranium nitricum6CH(1012)dilution factor were used to examine antihyperglycemic effects in streptozotocin induced diabetic rats. After 28 daysoftreatment,bodyweight, Hematology, Biochemistry (serum glucose, urea, creatinine, SGPT, SGOT, ALP, Triglyceride and HDL-cholesterol), Oral Glucose Tolerance Test, HbA1C with histopathologyof (Liver, Kidney, Pancreas) weremeasured.ResultsAfter Streptozotocin induction, the animals have shown significant increase in the fasting blood glucose level (p<0.01) as compared to normal control animals. Treatment with homeopathic medicine Insulinum 6CH, Pancreatinum 6CHandUranium nitricum6CHpotency showed significant decrease in levels of Glucose (p<0.05), OGTT, Total protein (P<0.001), ALP (P<0.05), Cholesterol (P<0.001), SGPT (P<0.001), SGOT (p<0.01), Urea, HbA1C as compared to diabetic animal.ConclusionsIn the present study homeopathic medicine Insulinum 6CH, Pancreatinum 6CH andUranium nitricum6CHpotency exhibitantihyperglycemic effects in streptozotocin induced diabetic rats.(AU)

Receptor Activator of Nuclear Factor-Kappa Ligand and Osteoprotegerin Expressions on Hyperglycemic Wistar Rats (Rattus Novergicus) During Orthodontic Tooth Movement

Abstract Objective: To investigate the differences of receptor activator of nuclear factor-κB ligand (RANKL) and Osteoprotegerin (OPG) expressions between normoglycemic and hyperglycemic Wistar rats (Rattus Novergicus) during Orthodontic Tooth Movement (OTM). Material and Methods: This study was true experimental with post-test group only. Thirty-two healthy male Wistar rats, weighted around 200-250 grams, 12-20 weeks old, were used as OTM animal study. They were divided into 2 groups (n=16), normoglycemic rats (normal blood glucose 80-120 mg/dl) and hyperglycemic rats (>250 mg/dl) induced by Streptozotocin with a dose of 30 mg in PBS injection intraperitoneally. A NiTi closed coil spring was mounted between maxillary first molar and incisors with the light force 10gf/mm2 in both groups to induce OTM. The studied animals were then terminated on days 1, 3, 6, and 9, respectively, and premaxilla was extracted. RANKL and OPG expression were examined utilizing immunohistochemistry (IHC) analysis. One-way ANOVA and Tukey HSD (p<0.05) were utilized to analyze the differences in the expression of RANKL and OPG between groups. Results: The hyperglycemic group on day 1, 9 rats showed a significant increase in the expression of RANKL, whereas OPG expression decreased significantly on days 1, 3, and 9. Conclusion: There was a significant increase of RANKL expression and a decrease of OPG expression in hyperglycemic rats as documented immunohistochemically.

Effects of ATRA on diabetic rats with renal ischemia-reperfusion injury

Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.

Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.

GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats

Abstract Purpose: To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms. Methods: Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed. Results: Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA. Conclusion: GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.

Macrophage migration inhibitory factor antagonist (p425) ameliorates kidney histopathological and functional changes in diabetic rats / Antagonista (p425) do fator de inibição da migração de macrófagos (MIF) melhora as alterações histopatológicas e funcionais renais em ratos diabéticos

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Swimming training potentiates the recovery of femoral neck strength in young diabetic rats under insulin therapy

OBJECTIVE: To test whether swimming training benefits femoral neck strength in young diabetic rats under insulin therapy. METHODS: A total of 60 male Wistar rats (age: 40 days) were divided equally into the following six groups: control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetes was induced with a unique intraperitoneal injection (60 mg/kg body weight) of streptozotocin. Seven days after the injection and after 12 hours of fasting, the animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, the animals in the exercise groups were subjected to progressive swimming training (final week: 90 min/day; 5 days/week; 5% load) for eight weeks. The animals in the insulin groups received a daily dose of insulin (2-4 U/day) for the same period. RESULTS: Severe streptozotocin-induced diabetes reduced the structural properties of the femoral neck (trabecular bone volume, trabecular thickness and collagen fiber content). The femoral neck mechanical properties (maximum load and tenacity) were also impaired in the diabetic rats. Insulin therapy partially reversed the damage induced by diabetes on the structural properties of the bone and mitigated the reductions in the mechanical properties of the bone. The combination of therapies further increased the femoral neck trabecular bone volume (∼30%), trabecular thickness (∼24%), collagen type I (∼19%) and type III (∼13%) fiber contents, maximum load (∼25%) and tenacity (∼14%). CONCLUSIONS: Eight weeks of swimming training potentiates the recovery of femoral neck strength in young rats with severe streptozotocin-induced diabetes under insulin therapy.