scholarly journals The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

2018 ◽  
Vol 19 (8) ◽  
pp. 2461 ◽  
Author(s):  
Özgür Can ◽  
Umut Üçel ◽  
Ümide Demir Özkay ◽  
Emel Ulupınar
Keyword(s):  
Cognitive Impairments ◽  
Memory Performance ◽  
Neuronal Loss ◽  
Cognitive Disorders ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Diabetes Model ◽  
Cornu Ammonis ◽  
The Central Nervous System ◽  
Treatment Of Diabetes

Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.

scholarly journals The Synergistic Effects of Ixeris dentata and Lactobacillus gasseri Extracts on a Diabetes-induced Dry Mouth Model by Enhancing Antioxidation

2020 ◽  
Author(s):  
Hwa Young Lee ◽  
Mingkun Gu ◽  
Jinhua Cheng ◽  
Joo Won Suh ◽  
Han-Jung Chae
Keyword(s):  
Synergistic Effects ◽  
Salivary Flow ◽  
Diabetic Rats ◽  
Dry Mouth ◽  
Oxidative Enzymes ◽  
Diabetic Patients ◽  
Aquaporin 5 ◽  
Diabetes Model ◽  
Streptozotocin Induced Diabetes ◽  
Ixeris Dentata

Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there was no way to relieve these symptoms. This study was aimed to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin-induced diabetes model, dry mouth condition was established as a model. Both control and diabetic rats were treated with a sublingual spray of either water or IXD and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na+/H+ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes; GSH:GSSG ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia.

scholarly journals Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Flora Reverchon ◽  
Vidian de Concini ◽  
Vanessa Larrigaldie ◽  
Sulayman Benmerzoug ◽  
Sylvain Briault ◽  
...  
Keyword(s):  
Cell Sorting ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Cognitive Impairments ◽  
Memory Performance ◽  
Cognitive Disorders ◽  
Fluorescence Activated Cell Sorting ◽  
Interleukin 33 ◽  
Inflammatory State ◽  
Deficient Mice

Abstract Background Interleukin (IL)-33 is expressed in a healthy brain and plays a pivotal role in several neuropathologies, as protective or contributing to the development of cerebral diseases associated with cognitive impairments. However, the role of IL-33 in the brain is poorly understood, raising the question of its involvement in immunoregulatory mechanisms. Methods We administered recombinant IL-33 (rmIL-33) by intra-hippocampal injection to C57BL/6 J (WT) and IL-1αβ deficient mice. Chronic minocycline administration was performed and cognitive functions were examined trough spatial habituation test. Hippocampal inflammatory responses were investigated by RT-qPCR. The microglia activation was assessed using immunohistological staining and fluorescence-activated cell sorting (FACS). Results We showed that IL-33 administration in mice led to a spatial memory performance defect associated with an increase of inflammatory markers in the hippocampus while minocycline administration limited the inflammatory response. Quantitative assessment of glial cell activation in situ demonstrated an increase of proximal intersections per radius in each part of the hippocampus. Moreover, rmIL-33 significantly promoted the outgrowth of microglial processes. Fluorescence-activated cell sorting analysis on isolated microglia, revealed overexpression of IL-1β, 48 h post-rmIL-33 administration. This microglial reactivity was closely related to the onset of cognitive disturbance. Finally, we demonstrated that IL-1αβ deficient mice were resistant to cognitive disorders after intra-hippocampal IL-33 injection. Conclusion Thus, hippocampal IL-33 induced an inflammatory state, including IL-1β overexpression by microglia cells, being causative of the cognitive impairment. These results highlight the pathological role for IL-33 in the central nervous system, independently of a specific neuropathological model.

Evaluation of the sub-chronic toxicity profile of the corm of Xanthosoma sagittifolium on hematology and biochemistry of alloxan-induced diabetic Wistar rats

2017 ◽  
Vol 14 (2) ◽  
Author(s):  
Olayinka A. Oridupa ◽  
Oluyemisi F. Folasire ◽  
Adedotun J. Owolabi
Keyword(s):  
Diabetes Mellitus ◽  
Wistar Rats ◽  
Chronic Toxicity ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Toxicity Profile ◽  
Xanthosoma Sagittifolium ◽  
Normal Rat ◽  
Treatment Of Diabetes

AbstractBackgroundHematological and biochemical changes associated with diabetes mellitus and probable reversal were assessed in alloxan-induced diabetic Wistar rats fed with varied percentages ofMethodsThe study had eight groups in all with group 8 (control) consisting of five normoglycemic rats fed with normal rat pellets (Nrp). Diabetes was experimentally induced by intraperitoneal injection of alloxan to normoglycemic rats. Diabetic rats (serum glucose >200 mg/dL) at 48 h postinjection were randomly divided into the seven groups, each diabetic group consisting of five rats. One group was untreated and fed with Nrp, four groups were fed with 25 %, 50 %, 75 % or 100 % Xs, one group was fed with 100 % Xs and administered with glibenclamide, while a 7th group was fed with Nrp and administered with glibenclamide.ResultsThis study shows that treatment of diabetes with corm ofConclusionscorm can be recommended for inclusion in diets of diabetics without causing further deterioration of health of the diabetic patients.

Piroxicam reduces acute and chronic pain response in type 1 diabetic rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abbas Alimoradian ◽  
Fatemeh Samimi ◽  
Hadise Aslfalah ◽  
Seied Amirhossein Latifi ◽  
Mehdi Salehi ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Normal Saline ◽  
Life Quality ◽  
Chronic Phase ◽  
Diabetic Rats ◽  
Effective Control ◽  
Diabetic Patients ◽  
Formalin Injection ◽  
Analgesic Effects

Abstract Objectives Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats. Methods In this study, we investigated the analgesic effects of drugs belonging to three different classes of NSAIDs in a rat model of diabetes. Four diabetic groups received normal saline, diclofenac, piroxicam and ketorolac, respectively, and four non-diabetic groups received normal saline, diclofenac, piroxicam and ketorolac. Type 1 diabetes was induced in rats by a single injection of streptozotocin (60 mg/kg bw). Formalin (50 µL of 2.5%) nociception assay was used to examine the effect of treatment with diclofenac, piroxicam and ketorolac on acute and chronic pain in healthy and diabetic rats. Results Piroxicam showed significant analgesic effects both in the acute phase of pain (5–10 min after injection of formalin into the left hind paw), and in the chronic phase (20–60 min after formalin injection) in healthy as well as diabetic rats. Diclofenac and ketorolac also reduced pain scores in healthy rats. However, these two drugs failed to diminish pain in diabetic rats. Conclusion Our data point for better efficacy of piroxicam in controlling pain in diabetes.

scholarly journals Beneficial Effects of Combination Therapy of Sitagliptin and β-carotene Drugs on Streptozotocin-induced Diabetic Rats

2020 ◽  
Vol 23 (2) ◽  
pp. 87-95
Author(s):  
Pulye Roy ◽  
Monirul Islam ◽  
Mohammad Saiful Islam ◽  
Mamunur Rashid
Keyword(s):  
Combination Therapy ◽  
Density Lipoprotein ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Fixed Dose ◽  
Diabetic Patients ◽  
Control Groups ◽  
Chronic Hyperglycemia ◽  
Serum Glutamate ◽  
Β Carotene

Diabetes mellitus (DM), characterized by chronic hyperglycemia is one of the most common chronic diseases affecting millions of people worldwide. A significant component of the risk associated with DM is thought to be because of its abnormal lipid ‘triad’ profile. All the associated complications are mainly due to imbalance between generation of free radicals and the antioxidant systems like catalase (CAT) and super oxide dismutase (SOD) enzymes. Moreover, increased level of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) are considered a consequence of hepatocyte damage. The current study was designed to investigate the antihyperglycemic and antidyslipidemic effects, oxidative stress and liver dysfunction indices of fixed dose combination therapy of sitagliptin [50 mg/70kg body weight (BW)] and β-carotene (5 mg/70kg BW) on streptozotocin (45 mg/kg BW) induced diabetic rats (SIDRs). The study showed that combination therapy induced a significant decrease in blood glucose level (BGL) from 19.09 ± 0.13 to 6.86 ± 0.11 mmol/l in comparison to the control group after daily treatment for three weeks. In case of dyslipidimic effect, combination therapy reduced total cholesterol (TC) (22.96%), triglycerides (TG) (17.54%) and low-density lipoprotein (LDL)-cholesterol (52.25%) levels significantly and increased high-density lipoprotein (HDL)-cholesterol level (55.98%) in comparison with respective diabetic control groups. We also observed that combination therapy lowered SGPT & SGOT level by 46.39% and 37.23%, respectively and increased SOD & CAT enzyme activity by 63.79% and 48.32%, respectively in comparison with diabetic control groups. These changes were significantly better than those of sitagliptin and β-carotene monotherapy. The suggestions of our findings of this research are that combination therapy is more potent than their individual monotherapy and may be beneficial for the treatment of diabetic patients with associated complications. Bangladesh Pharmaceutical Journal 23(2): 87-95, 2020

scholarly journals Effect of Polyherbal Mixtures on the Treatment of Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Aparajeya Panda ◽  
Somanatha Jena ◽  
Pramod Kumar Sahu ◽  
Sanghamitra Nayak ◽  
Payodhar Padhi
Keyword(s):  
Blood Glucose ◽  
Elevated Level ◽  
Treated Group ◽  
Diabetic Rats ◽  
Lipid Levels ◽  
Beneficial Effects ◽  
Estimated Parameters ◽  
Treatment Of Diabetes ◽  
Dose Levels ◽  
Elevated Lipid

The study focuses on polyherbal antidiabetic formulations of different plants used in the treatment of diabetes mixed in different concentrations. In the present study eleven medicinal plants with proven antidiabetic and related beneficial effects were selected for the preparation of five mixtures. The efficacy of prepared mixtures has been tested on streptozotocin- (STZ-) induced diabetic rats and compared with a commercially available drug glibenclamide. The mixtures at the dose levels of 400 mg/kg b.w. produced a significant decrease in blood glucose level by 69.6%, 70.97%, 64.45%, 71.82%, and 64.44% after 21 days of treatment. The elevated level of SGPT, SGOT, and ALP in the diabetic controlled group reflected the significant alteration of liver function by STZ induction and was found to be equipotent to glibenclamide in restoration of the elevated enzyme levels to normal. The elevated lipid levels (triglyceride and total cholesterol) were restored to near normal by these mixtures for all the estimated parameters. The results of the mixtures on treated group were found to restore the glycemic level to the near normal level thereby indicating antihyperglycemic activity of the formulated mixtures.

scholarly journals White Matter Integrity Disruptions Associated With Cognitive Impairments in Type 2 Diabetic Patients

Diabetes ◽  
2014 ◽  
Vol 63 (11) ◽  
pp. 3596-3605 ◽  
Author(s):  
Junying Zhang ◽  
Yunxia Wang ◽  
Jun Wang ◽  
Xiaoqing Zhou ◽  
Ni Shu ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Impairments ◽  
White Matter Integrity ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

FAMILIAL NONHEMOLYTIC JAUNDICE: BILIRUBINOSIS AND ENCEPHALOPATHY

PEDIATRICS ◽  
1969 ◽  
Vol 43 (3) ◽  
pp. 365-376
Author(s):  
William A. Gardner ◽  
Bruce W. Konigsmark
Keyword(s):  
Nervous System ◽  
Dentate Nucleus ◽  
Late Onset ◽  
Neuronal Loss ◽  
Bile Pigment ◽  
Histopathological Changes ◽  
Older Patient ◽  
Patient Case ◽  
The Central Nervous System ◽  
Original Report

The unique pathological findings of a case of congenital familial hyperbilirubinemia are presented. The patient (Case 3 of Crigler and Najjar's original report), although severely jaundiced, had developed normally without evidence of neurological disease until 15½ years of age. He then developed a progressive neurological deterioration which was clinically similar to infantile kernicterus. At autopsy most of his organs showed extensive intra- and extracellular deposition of bile pigment, particularly the renal papillae, atrial endocardium, intestinal mucosa, Kupffer cells of the liver, and the perivascular adventitia. Although no pigment was found in the central nervous system, there was striking neuronal loss and gliosis of the thalamus. Moderate neuronal loss was found in the putamen, caudate nucleus, dentate nucleus, and red nuclei. No histopathological changes were found in the hippocampus or cerebral cortex. It is suggested that the patient suffered from a late onset of "kernicterus" with involvement, in this older patient, of regions of the nervous system somewhat different from those in infantile kernicterus.

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats

2021 ◽  
pp. 1-19
Author(s):  
Jing-Hua Zhang ◽  
Hui-Zeng Yang ◽  
Hao Su ◽  
Jun Song ◽  
Yu Bai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Morphological Changes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Mild Stress ◽  
Ginsenoside Rb1 ◽  
Nissl Staining

Rhizoma coptidis(Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal’s depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

scholarly journals EGCG Prevents the Loss of Pontine Noradrenergic Neurons Induced by Diabetes: A Role in Diabetic Neuropathic Pain

2012 ◽  
Vol 18 (S5) ◽  
pp. 5-6 ◽  
Author(s):  
Carla Morgado ◽  
João Silva ◽  
André Miranda ◽  
Patrícia Pereira-Terra ◽  
Diogo Raposo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Diabetic Rats ◽  
Pain Modulation ◽  
Diabetic Patients ◽  
Spontaneous Pain ◽  
Noradrenergic Neurons ◽  
Diabetic Neuropathic Pain ◽  
Descending Pain Modulation ◽  
Pain Responses

Diabetes is a major health problem with an alarming increasing prevalence, and is the most frequent cause of neuropathy worldwide. Neuropathy affects 50–60% of diabetic patients, being a major life-quality impairment for a quarter of these patients. Diabetic neuropathic pain (DNP) is characterized by spontaneous pain, mechanical hyperalgesia and tactile allodynia and is accompanied by functional and neurochemical changes at the peripheral nerves, spinal cord and supraspinal pain control areas. Regarding the effects of diabetic neuropathy in the central somatossensory system, it was shown that streptozotocin (STZ)-diabetic rats present spontaneous hyperactivity and hyperexcitability of spinal nociceptive neurons, which may be subserving the exacerbated pain responses. The spinal functional changes and pain may be due to increased peripheral input(2), changes in spinal nociceptive modulatory mechanisms and altered supraspinal descending pain modulation. Noradrenergic descending pain modulation seems to be impaired since STZ-diabetic rats present decreased numbers of noradrenergic neurons at the A5 and A7 pontine cell groups, along with lower levels of noradrenaline at the spinal cord and higher behavioral responses to pain. This is consistent with the strong noradrenergic projection from A5 and A7 neurons to the spinal dorsal horn and the modulation of nociceptive transmission by local release of noradrenaline. The mechanisms underlying the decrease in noradrenergic neurons in the brainstem during diabetes remain unclear. Our recent findings that diabetes induces oxidative stress damage in neurons from those areas, lead us to hypothesize that it may contribute to their loss. Thereafter, with the present study we aimed to evaluate the effects of Epigallocathechin Gallate (EGCG), a potent antioxidant present in green tea, on spinal noradrenaline levels, on A5 and A7 noradrenergic neurons and on behavioral pain responses of STZ-diabetic rats.

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