Alloxan-diabetic Wistar Rats Research Articles

Effectiveness of durian peel ethanol extract for lowering blood sugar levels in alloxan diabetic wistar rats

High blood sugar levels can be influenced by several factors, including high-carbohydrate food consumption and a lack of physical activity. To minimize the side effects of hyperglycemic treatment, efforts have been made to explore anti-hyperglycemic compounds from other sources, such as durian peel (Durio zibetthinus Murr.). This study aimed to determine the effectiveness of ethanol extract from durian peel in lowering alloxan-induced blood sugar levels in Wistar rats (Rattus novergicus). The study is an experimental research employing an alloxan-induced diabetic rat model. The rats were divided into five different groups: Group I (negative control), Group II (positive control), Group III (dose 25 × 10–30/gBW), Group IV (dose 50 × 10–30/gBW), and Group V (dose 100 × 10–30/gBW). The durian peel used in this study was extracted using the maceration method with ethanol as the solvent. The results of this study indicate that ethanol extract from durian peel significantly reduced blood sugar levels after 10 to 15 days of durian peel extract administration (p < 0.05).

Study of the Antidiabetic Activity of Punica granatum L. Fruits Aqueous Extract on the Alloxan-Diabetic Wistar Rats.

Pancreatic β-cells dysfunction and impairment of insulin action usually leads to hyperglycemia. Punica granatum L. is a well-known traditional herbal remedy in Iran due to its positive effects on ameliorating blood glucose homeostasis. In this study, Alloxan-diabetic male Wistar rats were administrated with pomegranate fruits aqueous extract (PE) in different doses of 100, 200, and 350 mg/kg bw (PE+Da, PE+Db and PE+Dc, respectively), and the effects of PE polyphenols content on glucose metabolism in treated groups were examined using oral glucose tolerance test (OGTT), short-term and long-term PE consumption periods models followed by evaluation of plasma insulin, free fatty acids, and triglycerides levels and tissues contents of glycogen and triglycerides; compared with diabetic control (DC) and healthy control (NC) groups. By using Real-time PCR, the possibility of modulations of the Insulin receptor substrate 1 (IRS-1), Protein kinase B (Akt), Glucose transporter 2 and 4 (Glut-2, 4) mRNAs expression levels in PE treated rats were investigated. The obtained data showed noticeable reduction in fasting blood glucose (FBG) by 28.1% and 67.9% in short-term and long-term treatment models, respectively, in PE + Dc group. Also, there existed marked increase in the mRNAs expression levels of IRS-1, Akt, Glut-2, and Glut-4, which results in improvement of glucose uptake and promotes its storage. Taking together, it is suggested that PE administration contributes to the modulation of both hyperglycemia and hyperlipidemia in Alloxan-diabetic Wistar rats.

Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

Objective Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract (PGE) on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 (irs-1) mRNA in Alloxan-diabetic male Wistar rats. Materials and Methods In this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids (FFAs), triglycerides (TG), and glycogen compared with diabetic controls (DC)and normal controls (NC). We used real-time polymerase chain reaction (PCR) to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels. Results There was a noticeable reduction in fasting blood glucose (FBG) and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity. ConclusionPGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression.

Anti-hyperglycemic Effect of Khaya senegalensis Stem Bark Aqueous Extract in Wistar Rats

Aim: To investigate anti-hyperglycemic effect of aqueous extract of Khaya senegalensis stem bark (KSE) in alloxan-diabetic Wistar rats. Methodology: Thirty rats were randomly divided into six groups of 5 animals each. Group I (non-diabetic control) was given distilled water orally. Animals in the remaining five groups were treated with a single dose of alloxan (120mg/kg body weight, i.p) to induce diabetes mellitus. This resulted in significant increase in the fasting blood glucose level of the rats. Group I (non-diabetic control) and group II (hyperglycemic control) then received distilled water orally for 14 days. Group III, IV and V were treated orally with daily doses of 50, 100 and 150 mg/kg body weight of KSE respectively for 14 days. Group VI was given glibenclamide (5mg/kg, p.o) for the same period. Fasting blood glucose was determined by oxidative method in all the groups on day 0 (before treatment), day 7 and day 14. Oral glucose tolerance test and erythrocyte malondialdehyde (MDA) concentration were estimated after the two week treatment. Body weights of the animals were also measured on day 0, day 7 and day 14. Results: Treatment with KSE and glibenclamide caused significant (p<0.05) and dosedependent changes compared to the untreated animals with respect to body weight, blood glucose level and erythrocyte malondialdehyde (MDA) concentration. The antihyperglycemic effect of KSE was comparable to that of the standard drug, glibenclamide. Conclusion: The study showed that aqueous extract of Khaya senegalensis stem bark possesses anti-hyperglycemic activity.

Effects of Three Medicinal Plants Extracts in Experimental Diabetes: Antioxidant Enzymes Activities and Plasma Lipids Profiles inComparison with Metformin.

In the present study we aimed to evaluate the effects of methanolic extracts of the bulbs of Garlic (Allium sativum L., Alliaceae) and Persian shallot (Allium ascalonicum L., Alliaceae ) and leaves of Sage (Salvia officinalis L., Lamiaceae ), ASE, AAE and SOE respectively, on the antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) activities and on the levels of plasma lipids profiles such as triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) in Alloxan diabetic Wistar rats. In comparison with diabetic control rats in diabetic treated rats, AAE increases the activities of SOD (65%), GPX (43%) and CAT (55%). ASE and SOE increase SOD activity by 60% and 33% respectively. ASE reduces TC (34%), SOE decreases TG (40%) and LDL (30%) and AAE reduces VLDL (24%). Metformin exhibits mild antioxidant and hypolipidemic properties. Results of quantitative phytochemical analysis show that the methanolic garlic and Persian shallot bulbs extracts contain secondary metabolites including alkaloids (3.490% and 3.430%), glycosides (18.023% and 13.301%) and saponins (0.812% and 0.752%). Methanolic sage leaves extract contains flavonoids (1.014%), glycosides (23.142%) and saponins (2.096%). The total phenolic contents of ASE, AAE and SOE were in order 4.273, 3.621 and 6.548 mg GAE/g dry weight (DW). These results suggest that Allium sativum, Allium ascalonicum and Salvia officinalis are beneficial in the control of diabetes by noticeable antioxidant and hypolipidemic properties.

Vaccinium arctostaphylos, a common herbal medicine in Iran: Molecular and biochemical study of its antidiabetic effects on alloxan-diabetic Wistar rats

The purpose of this study was to define antidiabetic effects of fruit of Vaccinium arctostaphylos L. (Ericaceae) which is traditionally used in Iran for improving of health status of diabetic patients. Firstly, we examined the effect of ethanolic extract of Vaccinium arctostaphylos fruit on postprandial blood glucose (PBG) after 1, 3, 5, 8, and 24h following a single dose administration of the extract to alloxan-diabetic male Wistar rats. Also oral glucose tolerance test was carried out. Secondly, PBG was measured at the end of 1, 2 and 3 weeks following 3 weeks daily administration of the extract. At the end of treatment period the pancreatic INS and cardiac GLUT-4 mRNA expression and also the changes in the plasma lipid profiles and antioxidant enzymes activities were assessed. Finally, we examined the inhibitory activity of the extract against rat intestinal α-glucosidase. The obtained results showed mild acute (18%) and also significant chronic (35%) decrease in the PBG, significant reduction in triglyceride (47%) and notable rising of the erythrocyte superoxide dismutase (57%), glutathione peroxidase (35%) and catalase (19%) activities due to treatment with the extract. Also we observed increased expression of GLUT-4 and INS genes in plant extract treated Wistar rats. Furthermore, in vitro studies displayed 47% and 56% inhibitory effects of the extract on activity of intestinal maltase and sucrase enzymes, respectively. Findings of this study allow us to establish scientifically Vaccinium arctostaphylos fruit as a potent antidiabetic agent with antihyperglycemic, antioxidant and triglyceride lowering effects.

Experimental alloxan‐induced diabetes model in rats: lack of vascular dysfunction despite oxidative stress

Increased oxidative stress and reduced nitric oxide (NO) bioavailability are key features of diabetes mellitus that may result in vascular dysfunctions. We assessed whether an experimental model of alloxan‐diabetic Wistar rats promotes oxidative stress, reduces NO bioavailability and causes vascular dysfunction. After 1 week of alloxan injection (40 mg/Kg), rats with glycemia &gt; 200 mg/dl were considered diabetics (D). The weekly glycemia was significantly higher in D rats compared to control (C) (p &lt; 0.001). After 5 weeks of alloxan injection, plasma levels of malondialdehyde were increased in D compared to C rats (p = 0.002), however, plasma levels of nitrite and nitrate did not differ between the groups; this was accompanied by a significant reduction in endothelial NO synthase (NOS) immunostaining in endothelium (p = 0.001) and by a significant increase in inducible NOS immunostaining in adventitia of thoracic aorta from D rats (p &lt; 0.001). Moreover, the vascular reactivity study, performed in organ chambers, showed that the responsiveness of thoracic aortic rings to acetylcholine, sodium nitroprusside and phenylephrine was similar in both groups. Thus, these findings demonstrated that despite the development of diabetes and the increase in oxidative stress the 5 weeks duration of diabetes did not reduce NO bioavailability nor promoted vascular dysfunction in rats. Support: CAPES; FAEPA‐HC/FMRP.

Metformina interage com o treinamento físico diminuindo a glicemia e aumentando o armazenamento de glicogênio em ratos diabéticos

INTRODUÇÃO: Assim como em humanos, ratos diabéticos apresentam baixas quantidades de glicogênio. Entretanto, treinamento ou medicamentos podem causar diminuição da glicemia e melhorar o controle metabólico. Metformina aumenta o glicogênio enquanto diminui a glicemia em ratos normais estressados por exercício. OBJETIVO: Investigar se exercício regular e metformina melhoram o metabolismo de ratos diabéticos. MÉTODOS: Ratos Wistar diabéticos por aloxana tratados com metformina (DTM) ou não (DT) foram treinados. O treinamento consistiu de 20 sessões de 30 min de duração, cinco dias por semana. Ratos diabéticos sedentários foram usados como controle (SD e SDM). Metformina (5,6µg/ml) foi dada na água de beber. Após 48h de repouso, a glicose (mg/dl) e a insulina (ng/mL) foram medidas no plasma e o glicogênio (mg/100mg de tecido molhado) no fígado, sóleo e gastrocnêmio. RESULTADOS: A glicemia diminuiu de 435 ± 15 para 230 ± 20 no grupo DSM, para 143 ± 8,1 no grupo DT e para 138 ± 19mg/dl no grupo DTM. O grupo DSM teve proporcional aumento de glicogênio hepático de 1,69 ± 0.22 para 3,53 ± 0.24 e o treinamento aumentou para 3,36 ± 0,16mg/100mg. A metformina induziu aumento proporcional nos músculos sóleo de 0,21 ± 0,008 para 0,42 ± 0,03 e no gastrocnêmio, de 0,33 ± 0,02 para 0,46 ± 0,03, enquanto que o treinamento aumentou apenas no gastrocnêmio para 0,53 ± 0,03. Uma grande interação foi observada no fígado (o glicogênio aumentou para 6,48 ± 0,34). CONCLUSÃO: Pequenas doses orais de metformina e/ou treinamento restituíram parcialmente a glicemia e promoveram aumento de glicogênio em tecidos de ratos diabéticos. A associação com o programa de exercício foi benéfica, ajudando a diminuir a glicemia e a aumentar o armazenamento de glicogênio no fígado de ratos diabéticos.

Effects of aqueous extract of Ganoderma lucidum on blood glucose levels of normoglycemic and alloxan-induced diabetic wistar rats

Ganoderma lucidum mushroom has long been used as a potent medicinal plant in the far East, but its ethnomedicinal importance in Nigeria is yet to be fully realized. The effects of the aqueous extract on blood glucose levels of alloxan induced and normal Wistar rats have been investigated. Three doses of the extract (250, 500 and 1000 mg/Kg) were administered intraperitoneally. The dose of 250 mg/Kg of the extract did not significantly alter the blood glucose levels of both normal and alloxan induced diabetic Wistar rats. However, the doses of 500 and 1000 mg/Kg of the extract did significantly (p<0.05) decrease the blood glucose levels of alloxan diabetic Wistar rats at 4, 8 and 24 h. In normal rats, the dose of 1000 mg/Kg of the extract significantly (p<0.05) decrease the blood glucose levels at 8 and 24 h only. In conclusion, the dose of 1000 mg/Kg of the extract has shown both significant (p<0.05) hypoglycemic and anti-hyperglycemic effects in Wistar rats.

Integrated in vivo pharmacology using an instrumented, unrestrained and conscious rat platform: Application to rat models of diabetes

Introduction We define the technical and methodological aspects that led to a practical and reproducible biological in vivo platform allowing the measurement of more than 65 physiobiochemical parameters on a daily basis in freely moving conscious animals. Such a platform presents the ability to unleash incremental information in the hands of modern-day pharmacologists and physiologists. Methods To validate this platform, we fully characterized three rat models of Type 1 and Type 2 diabetes and their respective controls. Control, streptozotocin- and alloxan-diabetic Wistar rats in addition to ZDF- Lean and ZDF- Fatty rats were chronically implanted with an arterial catheter and kept in metabolic cages. The catheter was connected to a minipump infusing saline at a constant rate to maintain patency and used to collect blood and measure hemodynamic parameters on a daily basis. Results Catheter implantation was successful in over 95% of animals and catheter patency was successfully maintained for 30 days in about 75% of animals. The three diabetic rat strains showed elevations in food and water consumption, urinary output, plasma glucose, blood urea nitrogen, triglycerides and cholesterol. The two Type I models also showed a depressed body weight and hemodynamic function. The STZ model differed from the alloxan-model by elevations in liver enzyme activities (AST, ALT, and bilirubin) and a more severe dyslipidemia (triglycerides and total cholesterol). The ZDF- Fatty rats distinguished themselves by higher body weight and elevated white blood cell counts. Discussion This integrated platform represents a significant improvement in standard in vivo evaluations and could greatly improve the pace of development of potential new drugs.