Streptozotocin-diabetic Control Research Articles

Mitragyna Parvifolia- Effective Against Hyper Glycaemia, Proinflammatory Markers and Liver Apoptosis in Streptozotocin Induced Diabetic Rats

Background Ethanolic extract of Mitragyna pareidolia leaves were used as a traditionally use in the treatment of diabetic conditions. The aim of the current study was to find out the effect of Mitragyna pareidolia ethanolic leaves extract (MPE) on hyperglycemia developed by streptozotocin (STZ) induced type 2 diabetes in rats. Materials and Method An animal model of diabetes type 2 was developed by administration of STZ 90 mg/Kg to two-day old neonatal rat pups. Oral glucose test and parameters were examined of diabetic rat after the different dose of extracts. The rats were existing into following groups: Group I –Normal control, Group II – STZ diabetic control, Group III –STZ Diabetic –orally administered MPEx at doses of 300 mg/kg, Group IV STZ-Diabetic – orally administered at doses of 500 mg/kg, Our study was confirmed that 8 weeks chronic treatment with MPE in a dose dependent manner (300 and 500 mg/kg) reduced hyperglycemia and significantly increased serum insulin, C-peptide. Histology of liver was performed after sacrificing the rats with euthanasia. Result The ethanolic extract of MP was not show any acute toxicity up-to the dose of 2000 mg/kg and it was shown better glucose consumption in oral glucose tolerance test. Orally treatment of different doses of MP leaves extract decreased the level of serum glucose, reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. After the study, we found that elevated blood glucose and lipids were bring back to near normal. In addition, MPE also reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. Conclusion We conclude that MPE exerted antidiabetic effects and reduced its associated complications such as dyslipidemia and inflammation. HE and confocal image of TUNEL assay showed that MPE reduced inflammation and apoptosis in diabetic rats.

Butin Mitigates Memory Impairment in Streptozotocin-Induced Diabetic Rats by Inhibiting Oxidative Stress and Inflammatory Responses.

It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington's effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin.

Egg yolk oil accelerates wound healing in streptozotocin induced diabetic rats

ABSTRACT Impaired diabetic wound healing causes foot ulcers. We investigated egg yolk oil for skin wound healing in streptozotocin (STZ) induced diabetic rats. Rats were allocated into three groups of six. Group 1, nondiabetic control group, was treated topically with 2% fusidic acid ointment. Group 2, STZ diabetic control, was treated topically with 2% fusidic acid ointment. Group 3, STZ diabetic group, was treated topically with egg yolk oil. Three days after STZ injection, two full thickness excisional skin wounds were created on the back of each animal. Wound diameter was measured for 14 days and wound contraction was calculated. Re-epithelization time also was determined. Three rats from each group were sacrificed on experimental day 7 and the remaining rats on day 14. Wound samples were examined using hematoxylin and eosin, periodic acid-Schiff, Masson’s trichrome, Taenzer-Unna orcein and toluidine blue staining. Expression of endoglin (CD105), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were investigated using immunohistochemistry. Egg yolk oil increased the proliferation of epithelial cells and angiogenesis, and stimulated collagen deposition in the lesion area. Egg yolk oil increased CD105, EGF and VEGF expression in blood vessels, and EGF and VEGF expression in epidermis of the lesions. The predominant fatty acids in egg yolk oil are oleic, palmitic and linoleic, which likely were responsible for the beneficial effects of egg yolk oil on diabetic wound healing. Egg yolk oil appears to be a promising therapeutic agent for healing of diabetic wounds.

Leptin contributes to the beneficial effects of insulin treatment in streptozotocin-diabetic male mice.

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in β-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.

Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and antiapototic effects.

The Neuroprotective Effect of Cerebrolysin Against Type 1 Diabetes‐Induced Dementia In Rats

Cognitive decline and increased dementia are associated with diabetes. This work aimed to evaluate the potential neuroprotective effect of cerebrolysin (CBL) in modulating hippocampal alterations associated with streptozotocin (STZ) hyperglycemic complications. To this end, male Sprague Dawley rats were divided into (i) control (ii) CBL control (4 weeks) (iii) STZ diabetic control, and (iv) STZ + CBL (4 weeks). Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c) % level, which were associated by weight loss, elevation in serum tumor necrosis factor (TNF)‐α and decreased serum insulin like growth factor (IGF)‐1 levels. Furthermore, STZ caused learning and memory impairment that corroborated degenerative changes and neuronal loss in the hippocampus. Behavioral deficit was associated by changes in several neurotransmitter molecules. Moreover, diabetic rats showed an increase in hippocampal nitric oxide as well as thiobarbituric acid derivatives levels, however non‐protein thiols decreased. Though CBL did not affect STZ‐induced hyperglycemia, it partly improved body weight and HbA1c %. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas. CBL amended serum TNF‐α, IGF‐1, glutamate (GLU), serotonin (5‐HT) as well as oxidative biomarkers In conclusion, CBL possesses neuroprotection against diabetes‐associated cerebral neurodegeneration and cognitive decline via anti‐inflammatory and antioxidant effects as well as modulating hippocampal GLU and 5‐HT.

Antihyperglycemic and Antioxidant Activities of Medicinal Plant Stereospermum suaveolens in Streptozotocin-induced Diabetic Rats

The ethanol extract of Stereospermum suaveolens (EESS) bark was evaluated for its antihyperglycemic in addition to antioxidant effects in streptozotocin (STZ)-induced diabetic rats by acute and subacute models at dose levels of 200 and 400 mg/kg body weight, given orally. The ethanol extract showed a significant reduction in fasting blood glucose levels when compared to the standard drug, oral Glibenclamide (0.5 mg/kg body weight). The serum of rats treated with ethanol extract showed decreased levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, bilirubin, creatinine, urea, total cholesterol, triglycerides, and increased level of total proteins. EESS showed reduction in thiobarbituric acid reactive substances level and significantly increased the body weight (P < .001), glycogen, reduced glutathione, superoxide dismutase, and catalase activities, compared with STZ diabetic control in a dose-dependent manner. This finding shows that the ethanol extract of Stereospermum suaveolens exhibits potent antihyperglycemic and antioxidant properties.

Hypoglycaemic and antioxidant effects of onion, Allium cepa: dietary onion addition, antioxidant activity and hypoglycaemic effects on diabetic rats

The purpose of the present study was to discover the relative potency of onion, Allium cepa, with respect to its hypoglycaemic and hypolipidaemic effects on the diabetic situation, and the association of these effects with the potential against oxidative stress. Male Wistar rats were divided into four groups. A normal control (group A), and a non-diabetic group (group B) were treated daily with 1 ml A. cepa solution (0.4 g A. cepa/rat). Groups C and D were made diabetic by an intraperitoneal injection of streptozotocin (STZ) (60 mg/kg body weight) in citrate buffer (pH 6.3). These animals (groups C and D) were the STZ diabetic control and STZ diabetic rats with onion intake, respectively. Onion increased the fasting serum high-density lipoprotein levels, and demonstrated alleviation of hyperglycaemia in STZ diabetic rats. The hypoglycaemic and hypolipidaemic actions of A. cepa were associated with antioxidant activity, since onion decreased superoxide dismutase activities while no increased lipid hydroperoxide and lipoperoxide concentrations were observed in diabetic rats treated with A. cepa.

Effects of recurrent hyperinsulinemia with and without hypoglycemia on counterregulation in diabetic rats.

To understand the mechanisms whereby recurrent hypoglycemia increases the risk of subsequent hypoglycemia, it was necessary to differentiate the effects of recurrent hyperinsulinemia from those of hyperinsulinemic hypoglycemia. We examined basal and hypoglycemic endocrine function in normal rats, streptozotocin-diabetic controls, and diabetic rats exposed to 4 days of 2 episodes/day of hyperinsulinemic hypoglycemia (DH) or hyperinsulinemic hyperglycemia (DI). DH and DI rats differentiated the effects of hyperinsulinemia from those of hypoglycemia. In diabetic controls, basal plasma ACTH tended to be increased, and plasma corticosterone, plasma somatostatin, and pancreatic prosomatostatin and proglucagon mRNA were increased (P < 0.05) vs. normal rats. These parameters were normalized in DH and DI rats. In diabetic controls, glucagon, epinephrine, norepinephrine, corticosterone, and peak glucose production responses to hypoglycemia were reduced (P < 0.05) vs. normal rats. In DI rats, epinephrine responses were normalized. Conversely, DH rats displayed marked further impairment of epinephrine and glucose production responses and increased peripheral insulin sensitivity (P < 0.05 vs. diabetic controls). Both insulin regimens partially normalized glucagon and fully normalized norepinephrine and corticosterone responses. In summary, recurrent hyperinsulinemia in diabetic rats normalized most pituitary-adrenal, sympathoadrenal, and pancreatic parameters. However, concurrent hypoglycemia further impaired epinephrine and glucose production responses and increased insulin sensitivity. We conclude that 1) recurrent hypoglycemia may increase the risk of subsequent hypoglycemia by increasing insulin sensitivity, and 2) epinephrine counterregulation is particularly sensitive to impairment by recurrent hypoglycemia.