Streptozocin Administration Research Articles

DEVELOPMENT OF PATHOLOGICAL CHANGES IN THE ORAL CAVITY ORGANS OF ANIMALS UNDER CONDITIONS OF POLYNEUROPATHIES OF DIFFERENT GENESIS

The aim of our research is to study the effect of polyneuropathy of different genesis on the development of pathological changes in the large salivary glands and periodontal tissues of animals. Methods. The study was conducted on 62 laboratory rats of both sexes. Toxic polyneuropathy was induced by paclitaxel injection, experimental type 1 diabetes mellitus was modeled by streptozocin injection, and alcoholic polyneuropathy was induced by chronic administration of increasing concentrations of ethanol. The development of polyneuropathy was confirmed by a change in the the pain sensitivity threshold (PST) using the Randall-Selitto tensoalgometric method. In the homogenate of oral cavity organs, total proteolytic and total antitryptic activity, catalase activity, content of TBARS, average mass molecules, oxidatively modified proteins, fucose and glycosaminoglycans (GAG), and amylase activity were determined. The level of total, protein-bound and non-protein sulfhydryl groups, activity of superoxide dismutase, glutathione peroxidase, glutathione transferase, glutathione reductase; content of reduced and oxidized glutathione, diene conjugates and Schiff bases were determined in blood serum. Results. We established the increasing of PST in animals that were simulated neuropathies of different genesis. All three types of polyneuropathies are accompanied by the development of carbonyl-oxidative stress in the soft tissues of the periodontium and large salivary glands of rats, which is evidenced by a probable increase in the content of oxidatively modified proteins and the content of TBARS, as well as average mass molecules compared to these indicators in intact animals . Under the conditions of modeling all three polyneuropathies, the protein-synthetic activity in the large salivary glands is suppressed, as evidenced by a decrease in the activity of α-amylase. Under conditions of experimental diabetic and toxic neuropathy in the salivary glands of animals, changes in the proteinase-inhibitor balance of the compensatory type are observed. We found that polyneuropathies of different genesis cause increased catabolism of biopolymers of the extracellular matrix of the periodontal connective tissue of rats, which confirms the increase in the content of GAG and fucose compared to these indicators in control animals. Conclusions. Under conditions of diabetic, toxic and alcoholic neuropathy, the amylolytic activity of the large salivary glands of animals is suppressed, the balance of the pro- and antioxidant system changes. When modeling peripheral polyneuropathy in animals by administration of paclitaxel, streptozocin, and ethanol, the development of periodontal syndrome is observed, the leading pathogenetic mechanisms of which are increased catabolism of connective tissue glycoconjugates and the development of oxidative stress and proteinase-inhibitor imbalance.

Comparative effects of curcumin versus nano-curcumin on histological, immunohistochemical expression, histomorphometric, and biochemical changes to pancreatic beta cells and lipid profile of streptozocin induced diabetes in male Sprague–Dawley rats

Diabetes mellitus is a worldwide problem characterized by hyperglycemia as well as the damage of the microscopic structure of the beta cells of Langerhans pancreatic islets. In the present study, the histological, immunohistochemical, morphometric, and biochemical alterations to pancreatic beta cells in streptozocin (STZ)-induced diabetes were assessed in rats treated with curcumin (CU) (100 mg/kg/day) or nano-curcumin (nCU) (100 mg/kg/day) for 1 month. Twenty-four adult male Wistar albino rats were distributed into four groups: the nondiabetic control group, the diabetic untreated group, and two diabetic groups treated with CU or nCUR, respectively. Blood glucose, serum insulin levels, and lipid profile were measured. The pancreatic tissues were collected and processed into paraffin sections for histological and immunohistochemical examination, oxidative stress markers, and real-time PCR expression for pancreatic and duodenal homeobox 1 (PDX1). The insulin expression in beta cells was assessed using immunohistochemistry. Morphometrically, the percentage area of anti-insulin antibody reaction and the percentage area of islet cells were determined. STZ-induced deteriorating alteration in beta cells led to declines in the number of functioning beta cells and insulin immunoreactivity. In STZ-treated rats, CU and nCUR significantly reduced blood glucose concentration while increasing blood insulin level. It also caused a significant increase in the number of immunoreactive beta cells to the insulin expression and significant reduction of the immunoreactive beta cells to the caspase-3 expression. In conclusion, CU and nCUR could have a therapeutic role in the biochemical and microscopic changes in pancreatic beta cells in diabetes-induced rats through STZ administration with more bio-efficacy of nCUR.

Effect of Selenium Nanoparticles and/or Bee Venom against STZ-Induced Diabetic Cardiomyopathy and Nephropathy.

The main purpose of our study was to examine the role of selenium nanoparticles (SeNPs) and/or bee venom (BV) in ameliorating diabetic cardiomyopathy (DCM) and nephropathy (DN) at the biochemical, histopathological and molecular levels. Fifty male albino rats were used in this experiment, divided into five groups: control, Streptozocin (STZ) diabetic, STZ-diabetic treated with SeNPs, STZ-diabetic treated with BV, and STZ-diabetic treated with SeNPs and BV. Biochemically, STZ injection resulted in a significant increase in serum glucose, BUN, creatinine, CRP, CK-MB, AST, LDH and cardiac troponins with a significant decrease in the serum insulin and albumin concentrations. Histopathologically, STZ injection resulted in diabetes, as revealed by glomerulonephritis, perivascular hemorrhage, inflammatory cell infiltrations and fibrosis, with widening of interstitial spaces of cardiomyocytes, loss of muscle cells continuity and some hyaline degeneration. At the molecular levels, the expression levels of miRNA 328, miRNA-21, TGFβ1, TGFβ1R, JAK1, STST-3, SMAD-1 and NFκβ genes were significantly up-regulated, whereas the expression levels of SMAD-7 were significantly down-regulated. It is concluded that SeNPs and/or BV administration ameliorates the deleterious effects resulting from STZ administration through improving the biochemical, histopathological and molecular effects, suggesting their protective role against the long-term diabetic complications of DCM and DN.

Antidiabetic and antioxidant potential of total extract and supernatant fraction of the roots of Anogeissus leiocarpus in HFD-fed and Streptozocin -induced diabetic rats

The aim of this study was to evaluate the antidiabetic properties of hydro alcoholic extract and supernatant fraction of the roots of Anogeissus leiocarpus, a plant used by traditional healers to treat Diabetes mellitus. Diabetes mellitus was induced by a single intraperitoneal administration of Streptozocin to Sprague Dawley rats under a fructose-enriched fat diet. Diabetic rats were treated with 500 mg/kg of total extract and 100 mg/kg of supernatant. The antidiabetic activity was assessed by measuring blood glucose level, lipid profile, insulin and biochemical parameters together with the antioxidant potential.The administration of total extract and supernatant exhibited significant decrease (p < 0.01) of the blood glucose level in the diabetic rats after 7 days of treatment compared to the diabetic rats. A significant reduction in the serum concentrations of cholesterol (19.7 %) and triglycerides (56.7 %) was observed in the treated diabetic rats. The levels of insulin did not differ across all the groups. However, compared to diabetic rats, HOMA-IR (Homeostasis Model Assessment for Insulin-resistance) and HOMA-β (Homeostasis Model Assessment for β cell function) showed a statistical decrease in insulin resistance and an increase in pancreatic β cell function in the treated diabetic rats. Moreover, total extract and supernatant significantly increased GSH level and decreased lipid peroxidation because of their antioxidant properties. In comparison, the supernatant fraction exerted stronger antidiabetic and antioxidant effects than the total extract.Hence, the roots of Anogeissus leiocarpus are a potent antidiabetic agent that can be developed as an alternative medicine for diabetes and its complications.

Litsea polyantha Extracts Ameliorate Diabetes and Oxidative Stress in Streptozocin-induced Diabetic Rats

Published on:August 2022Journal of Young Pharmacists, 2022; 14(3):289-294Original Article | doi:10.5530/jyp.2022.14.57 Authors:Waseem Khan1, Jaya Sharma1, Sanjay Singh2, Pankaj Sharma11School of Pharmaceutical Sciences, Department of Pharmacy, Apex University, Rajasthan, INDIA.2Siddhartha Institute of Pharmacy, Dehradun, Uttarakhand, INDIA. Abstract: Objectives: Litsea polyantha (LP) is a traditional medicinal plant in India. As the bark is mildly astringent, it is traditionally used to treat diarrhoea. Powdered bark and roots are used for pain, bruises, contusions, and fractures in animals. Litsea polyantha was evaluated for its blood glucose lowering abilities as well as for its ability to curb oxidative stress. Methods: In Wistar rats, diabetes was induced by intraperitoneal administration of Streptozocin (STZ) (60 mg/kg, b.w) for four weeks. After clipping the rats’ tails, blood glucose levels were determined. Body weight and urine volume were also measured. In addition, oxidative stress markers such as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured. Biochemical estimations were further strengthened by histological evaluation. The statistical analysis of results was carried out using one-way analysis of variance (ANOVA), followed by Tukey’s post hoc with GraphPad Prism software package. Results: Compared to untreated diabetic rats, LP extracts significantly decreased blood glucose levels in diabetic rats for 4 weeks. As evidenced by the glucose levels and biochemical markers, diabetes has significantly improved. LP treated diabetic rats had significantly higher levels of antioxidant defence enzymes and lower levels of TBARS. STZ-induced elevation of glucose levels in diabetic rats was prevented by LP. Conclusion: The results of this study demonstrated that LP had antioxidative and anti-inflammatory properties that might contribute to its therapeutic effects on diabetic rats.Keywords: Litsea polyantha, Diabetes, Oxidative stress, Inflammation, Antioxidant.

Abstract P3047: Identification Of Role Of Intracellular Chloride Channel Clic4 In Diabetic Cardiomyopathy.

Cardiovascular diseases are the most common cause of morbidity and mortality in Diabetic patients. Mitochondrial dysfunction is the major contributor of the myocardial structural, functional, and metabolic defects in diabetic cardiomyopathy. Activation of mitochondrial ion channel, K ATP have been shown to facilitate protection from the adverse effects of diabetic cardiomyopathy via modulating mitochondrial function. In this study we delineate the impact of mitochondrial associated membrane (MAM) chloride channel-CLIC4 in diabetic cardiomyopathy. Our results show that pharmacological inhibition of chloride intracellular channel (CLIC) with IAA-94 abrogated the cardio-deleterious effects of hyperglycemia in neonatal cardiomyocytes, thus, implicating role of targets of IAA-94 in the onset and development of diabetic cardiomyopathy. Amongst the six mammalian paralogs of CLICs, we identified CLIC4 and CLIC5 are most abundant in the heart. In addition, we observed over expression and localization changes of MAM-CLIC4 but not mitochondrial CLIC5 in neonatal cardiomyocytes upon high glucose treatment. Furthermore, cardiomyocytes isolated from CLIC4 knock out mice under hyperglycemia do no exhibit disruption of sarcomere structures, reduction in contractility, and enhanced ROS production in comparison to wild type cardiomyocytes. These observations suggest that an absence of CLIC4 revokes the structure-function changes in cardiomyocytes upon hyperglycemia. Moreover, we demonstrate that clic4 -/- mice were protected from body weight gain and impaired glucose tolerance in comparison to wild type mice in the presence of a high fat diet. Interestingly, we also observed that clic4 -/- mice are resistant to increase in blood glucose levels upon streptozocin administration. Thus, suggesting a regulatory role of CLIC4 in glucose metabolism. Overall, this study suggests a probable novel role of intracellular chloride channel CLIC4 in diabetic cardiomyopathy via regulating glucose metabolism.

Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mg/kg and 400 mg/kg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (p < 0.001) during the elevated plus maze (EPM) test. The novel object recognition (NOR) test revealed a longer exploration time (p > 0.05) with novel objects and a higher discrimination index (p > 0.05). The Y-maze test also showed a significant increase in the number of entries to the novel arm (p > 0.05) and the total number of entries in the trial (p > 0.01) as well as in test (p > 0.05) sessions. Reduction in blood glucose (p > 0.05) and improvement in blood insulin (p > 0.05) levels were also noted. Improvement in ACh levels (p > 0.001) with 400 mg/kg of ASSE and reduction in AChE (p > 0.001) with both doses of ASSE were also observed in the brain homogenates. The results of ASSE were found comparable with the metformin-treated rats. The estimation of phytochemical constituents displayed a significant presence of phenolic content. Further, molecular modeling studies showed ellagic acid, catechin, and epicatechin as the potential molecule interacting with GSK-3β, α-amylase, and AChE and may be responsible for observed bioactivity. In conclusion, ASSE has the ability to alleviate T2DM-related cognitive impairments.

Tert-Butylhydroquinone alleviates insulin resistance and liver steatosis in diabetes.

OBJECTIVES:This work aimed to determine tert-Butylhydroquinone (TBHQ)'s effects on insulin resistance (IR) and liver steatosis in diabetic animals and to explore the underpinning mechanisms.MATERIALS AND METHODS:Male ApoE-/-mice underwent streptozocin (STZ) administration while receiving a sucrose/fat-rich diet for type 2 diabetes mellitus (T2DM) establishment. This was followed by a 6-week TBHQ administration. Body weight, fasting (FBG) and postprandial (PBG) blood glucose amounts, and insulin concentrations were measured, and the oral glucose tolerance test (OGTT) was carried out. Hematoxylin and eosin (H and E) staining and immunoblot were carried out for assessing histology and protein amounts in the liver tissue samples. In addition, cultured HepG2 cells were administered HClO and insulin for IR induction, and immunoblot was carried out for protein evaluation. Finally, the cells were stained with the Hoechst dye for apoptosis evaluation.RESULTS:The model animals showed T2DM signs, and TBHQ decreased FBG, ameliorated glucose tolerance and reduced liver steatosis in these animals. In addition, TBHQ markedly upregulated AMPKα2, GLUT4 and GSK3 β, as well as phosphorylated PI3K and AKT in the liver of mice with T2DM. In agreement, TBHQ decreased HClO-and insulin-related IR in cells and suppressed apoptosis through AMPKα2/PI3K/AKT signaling.CONCLUSIONS:TBHQ alleviates IR and liver steatosis in a mouse model of T2DM likely through AMPKα2/PI3K/AKT signaling.

Drp1 knockdown represses apoptosis of rat retinal endothelial cells by inhibiting mitophagy

Diabetic retinopathy (DR) is the leading clinical cause of blindness in diabetic patients. Mitophagy participates in the pathogenesis of DR. Dynamin related protein 1 (Drp1) is associated with mitophagy. Here, we investigated whether Drp1 can regulate mitophagy to affect the progression of DR. We constructed DR rat model by administration of streptozocin. Primary rat retinal endothelial cells (RECs) were treated with high glucose (HG) as a DR cell model. Drp1 was highly expressed in the retinal tissues of DR rats and HG-treated RECs. Drp1 knockdown inhibited HG-mediated increase of reactive oxygen species (ROS) levels and apoptosis in RECs. Moreover, Drp1 silencing inhibited the expression of autophagy-related proteins LC3-II/LC3–1 and Beclin-1 and reduced LC3 puncta in HG-treated RECs. The expression of mitochondrial marker Tom20 was reduced and the levels of mitophagy were increased in the HG-treated RECs, which was rescued by Drp1 silencing. Drp1 knockdown repressed LC3-II expression in HG-treated RECs, indicating that autophagy flux was inhibited. Rapamycin (autophagy activator) enhanced ROS levels and apoptosis in HG-treated RECs by activating autophagy, which was rescued by Drp1 knockdown. In conclusion, these data demonstrated that Drp1 knockdown repressed apoptosis of rat retinal endothelial cells by inhibiting mitophagy. Thus, this work suggests that targeted regulation of Drp1 may become a treatment for DR.

The anti-diabetic effects of betanin in streptozotocin-induced diabetic rats through modulating AMPK/SIRT1/NF-\u03baB signaling pathway

BackgroundIn the last few years, the effects of bioactive food components have received much attention because of their beneficial effects including decreasing inflammation, scavenging free radicals, and regulating cell signaling pathways. Betanin as a potent antioxidant has been previously reported to exhibit anti diabetic effects. The present study aimed to evaluate the effects of betanin on glycemic control, lipid profile, hepatic function tests, as well as the gene expression levels of 5′ adenosine monophosphate‑activated protein kinase (AMPK), sirtuin-1 (SIRT1), and nuclear factor kappa B (NF‑κB) in streptozocin (STZ) induced diabetic rats.MethodsDiabetes was induced in male Sprague–Dawley rats by intraperitoneal administration of STZ. Different doses of betanin (10, 20 and 40 mg/kg.b.w) was administered to diabetic rats for 28 days. Fasting blood glucose and serum insulin were measured. The histopathology of liver and pancreas tissue evaluated. Real-time PCR was performed to assess gene expression levels.ResultsTreatment of diabetic rats with betanin (10 and 20 mg/kg.b.w) reduced FBG levels compared to the control diabetic rats (P < 0.001). Betanin at the dose of 20 mg/kg.b.w was most effective in increasing serum insulin levels (P < 0.001) improving glucose tolerance test (GTT) as well as improvement in lipid profile and liver enzymes levels. According to histopathologic assay, different damages induced by STZ to liver and pancreas tissues was largely eliminated by treatment with 10 and 20 mg/kg.b.w of betanin. Betanin also significantly upregulated the AMPK and SIRT1 and downregulated the NF-κB mRNA expression compared to the diabetic control rats (P < 0.05).ConclusionBetanin could modulate AMPK/SIRT1/NF-κB signaling pathway and this may be one of its anti-diabetic molecular mechanisms.

Effects of malathion exposure on glucose tolerance test in diabetic rats; emphasis on oxidative stress and blood concentration of malathion by gas chromatography mass spectrometry

Malathion is one of the widely used broad-spectrum organophosphate insecticides (OPI) in Iran. Malathion affects carbohydrate metabolism, causes hyperglycemia and increases the risk of diabetes. The present study was undertaken to investigate the potential of malathion to exacerbate diabetes-induced oxidative stress and impairment in blood glucose level and glucose tolerance in a sub-acute study. Malathion concentration in blood analyzed with gas chromatography mass spectrometry (GC-MS) after sample preparation of blood samples based on magnetic Fe3O4-supported graphene oxide (Fe3O4@ GO) nanoparticles. Type 1 diabetes was experimentally induced by intraperitoneal administration of streptozocin (65 mg kg-1). Diabetic and non-diabetic rats were treated with malathion at the dose of 150 mg kg-1day-1 or 0.5-4.0 mg L-1 in blood for 4 weeks. Fasting blood glucose was measured every week. At the end of the study, blood samples were investigated for markers of oxidative stress. Exposure to multiple doses of malathion decreased the total antioxidant capacity of plasma and the activity of catalase and superoxide dismutase enzymes in diabetic rats. Blood glucose and glucose tolerance test (GTT) and oxidative damages did not change significantly in diabetic rats exposed to malathion. However, malathion concentration in blood caused to increase GTT in malathion-treated non-diabetic rats.

Anti-hyperglycemic effects of dihydromyricetin in streptozotocin-induced diabetic rats

Dihydromyricetin (DHM), as a bioactive flavanonol compound, is mainly found in “Tengcha” (Ampelopsis grossedentata) cultivated in south of China. This study aimed to investigate the anti-hyperglycemic and anti-dyslipidemic activities of DHM using type 2 diabetes mellitus (T2D) rats, which was induced by feeding with high fat and fructose diet for 42 days and intraperitoneal administration of streptozocin. Forty-eight freshly-weaned rats were randomly assigned into the negative control (Blank), low dose (100mg/kg), medium dose (200mg/kg), high dose (400mg/kg), and positive (40mg/kg, met) groups. Fasting blood glucose and body weight were measured at weekly interval. Oral glucose tolerance tests were performed on days 42. The results revealed that DHM possessed significant antihyperglycaemic and antihyperinsulinemic effects. Moreover, after the DHM treatment, p-Akt and p-AMPK expression was upregulated, and glycogen synthase kinase-3β (GSK-3β) expression was downregulated, indicating that the potential anti-diabetic mechanism of DHM might be due to the regulation of the AMPK/Akt/GSK-3β signaling pathway.

Ameliorative Effect of &amp;lt;i&amp;gt;Moringa Oleifera&amp;lt;/i&amp;gt; Biochemical Constituents on Blood Glucose Level of Streptozocin-Induced Diabetic Wistar Rats

Medicinal plants are among the important source of potential therapeutic agents for diabetes. Therapeutic use of <i>Moringa oleifera</i> leaf extract has been practiced in management of diabetes because of its potential to decrease blood glucose and lipids concentration after ingestion. This study was conducted to evaluate the ameliorative effect of <i>Moringa oleifera </i>leaf extract on streptozocin induced diabetes Wistar rats. Initially, diabetes was induced by given streptozocin (STZ) intravenously followed by the treatments with different concentration of<i> Moringa oleifera</i> aqueous leaf extract. Fasting blood glucose level was measured using Accu-Chek glucometer after 24, 48, 72 and 97 hours post treatment. There is significance difference at 0.05 in blood glucose level between the control groups and the groups that were treated with the leaf extract after administration of STZ. Hence, this plant shows high potential to be used in the management of hyperglycaemia. The need for the toxicity study to evaluate it effect in body tissues and organs is recommended. There is need to study the phytochemical constituents to identify the bioactive lead compound with ameliorative effect.

BASIC PRINCIPLES AND METHODS OF MODELING HYPOGONADISM: A LITERATURE REVIEW

Purpose: To consider the basic principles and methods of experimental modeling of hypogonadism in laboratory animals, to define the main benefits and drawbacks of each separate method in hypogonadism modeling. Materials and methods: We analyzed modern foreign and domestic literature using the following databases: PubMed / Medline, Embase, Google Scholar. Results: Presently, there are three main principles of modeling hypogonadism: surgical, genetic, and pharmacological. The principle of surgical modeling of hypogonadism is based on the removal of the gonads, or on the temporary imposition of a suture on the distal section of the spermatic cord, which leads to occlusion of the testicular artery that feeds the gonads. The principle of genetic modeling of hypogonadism is to induce mutations in the genes encoding the most important regulatory molecules, in particular kisspeptin, neurokinin B, and their receptors in laboratory animals. The principle of pharmacological modeling of hypogonadism is based on the administration of streptozocin to laboratory animals, which has a toxic effect on the gonads and pancreas. Conclusion: Hypogonadism represents a very common pathological condition that affects many organs and tissues. Therefore, the use of experimental models of hypogonadism to study fundamental pathophysiological and pathomorphological processes is a relevant research area. Each principle of hypogonadism modeling is unique in its own way, exhibits advantages and disadvantages, and allows the creation of specific conditions necessary for the development of hypogonadism in laboratory animals. Taking into account the numerous beneficial effects of testosterone on many cells and tissues of the human body, it becomes obvious that experimental models of hypogonadism can be in demand for many medical spheres.

The Protective Effect and Mechanism of Dexmedetomidine on Diabetic Peripheral Neuropathy in Rats.

ObjectiveTo investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage.MethodsEighty male Sprague-Dawley (SD) rats were randomly allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine treated group (YOH group). DPN was induced by intraperitoneal administration of streptozocin (STZ) (35 mg/kg). The body weights, blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the motor, and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured. Then the sciatic nerve was isolated for H&E staining and immunohistochemical staining. The oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD), and glutathione peroxidase (GSH-Px) and apoptosis related cytokines such as Bax, Bcl-2, and caspase-3 were estimated.ResultsThere was no significant difference of the blood glucose and body weight among the DPN group, DEX group, and YOH group. H&E staining showed that DEX treatment can ameliorate the damage of sciatic nerve cells. In the DPN group, MWT, TWL, MNCV, and SNCV were significantly reduced compared with the C group (P < 0.05). In DEX group rats, MWT, TWL, MNCV, and SNCV were increased significantly (P < 0.05) compared with the DPN group and YOH group rats. Lower SOD and GSH-Px, and higher MDA were found in the DPN group compared with the C group (P < 0.01), and DEX treatment restored SOD, GSH-px, and MDA activity significantly (P < 0.01). The expression levels of Bax and caspase-3 were increased, while that of Bcl-2 was decreased significantly in the DPN group compared with the C group (P < 0.05). In the DEX group, the expression levels of Bax and caspase-3 were decreased significantly (P < 0.05), while that of Bcl-2 was increased significantly (P < 0.05) compared with the DPN group and the YOH group.ConclusionThe results of this study demonstrated that DEX has the inhibitory and protective effects on DPN of rats. This may be associated with its antioxidative and anti-apoptosis responses.

Influence of Angiotensin Receptor Blocker (Candesartan) and Angiotensin-Converting-Enzyme Inhibitor (Enalapril) Combined with Glimepiride on Glycated Hemoglobin in Non-Insulin Dependent Diabetic Rats (NIDDM)

Background: Antihypertensive agents like Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Converting Enzyme Blockers (ARBs) are commonly indicated for patients with both hypertension and diabetes. However, the effect of these agents on blood sugar level or glycated hemoglobin (HbA1c) is still controversial. This study aims at investigating the short, and long term effects of ACEIs and ARBs on blood sugar level and HbA1c of a group of streptozocin (STZ)-induced NIDDM rats when given in combination with Glimepiride (antidiabetic drug from Sulfonylureas group).&#x0D; Methods: Diabetes mellitus (DM) was induced in 100 Wistar albino adult male and female laboratory rats above 8 weeks old, and weigh between 250-300 gm by the administration of Streptozocin 75% α-anomer. Two weeks later, the 100 rats were then randomized into four groups (25 rats each). Group one was the untreated control group (received placebo only), while other groups (II, III, and IV) were treated by Glimepiride only, Glimepiride plus ARB (Candesartan), and Glimepiride plus ACEI (Enalapril) respectively. HbA1C levels were measured at baseline (pre-test/directly after randomization) to ensure that there was no significant difference between study groups at the baseline, post-test (after two weeks), and delayed-post-test (12 weeks after randomization/ 10 weeks after post-test) to measure short and long-term changes in the study groups.&#x0D; Results: There was no significant difference (p-values &gt;0.05) between the four groups (groups I, II, III, and IV) in the HbA1C mean level at the beginning of this study (two-weeks after randomization and injection of STZ) (mean = 7.62 ±SD = 0.41, 7.72 ±SD = 0.48, 7.66 ±SD = 0.47, and 7.52 ±SD = 0.51respectively). However, two weeks later, treated groups (groups II, III, and IV) showed moderate reduction of HbA1C mean level compared to the untreated (placebo) group I, that was significant in groups III, and IV, and insignificant in group II (mean =7.43±SD 0.54, 6.97±SD 0.33, 6.72±SD 0.26, and 7.71 ±SD 0.44 respectively). Furthermore, treated groups (groups II, III, and IV) showed significant dramatic reduction of HbA1C mean level when compared to the untreated group (group I) (mean = 6.22 ±SD 0.51, 5.24 ±SD 0.62, 5.22 ±SD 0.13, and 7.62 ±SD 0.42 respectively).Overall, treated groups showed significantly lower HbA1C level than placebo groups. Moreover, Glimepiride + Enalapril combination showed a stronger hypoglycemic effect than the Glimepiride + Candesartan combination at post, and post-delayed tests, however, these differences were not significant.&#x0D; Conclusion: The addition of either ACEIs like Enalapril, or ARBs like Candesartan to Sulfonylureas like Glimepiride to in NIDDM patients will synergize its anti-diabetic effect in NIDDM subjects, and might increase the possibility of hypoglycemia. Caution and/or dose adjustment should be considered upon using these agents together in patients with hypertension along with diabetes.

C-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Objective Mesenchymal stem cells (MSCs) are considered a promising therapy for wound healing. Here, we explored the role of c-Jun in diabetic wound healing using human umbilical cord-derived MSCs (hUC-MSCs). Methods Freshly isolated hUC-MSCs were subjected to extensive in vitro subcultivation. The cell proliferative and migratory capacities were assessed by the Cell Counting Kit-8 and scratch assays, respectively. c-Jun expression was evaluated by RT-PCR and western blot analysis. The function of c-Jun was investigated with lentivirus transduction-based gene silencing and overexpression. Diabetes mellitus was induced in SD rats on a high-glucose/fat diet by streptozocin administration. Wounds were created on the dorsal skin. The effects of c-Jun silencing and overexpression on wound closure by hUC-MSCs were examined. Reepithelialization and angiogenesis were assessed by histological and immunohistochemical analysis, respectively. Platelet-derived growth factor A (PDGFA), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) levels were determined by western blot analysis. Results hUC-MSCs showed gradually decreased cell proliferation, migration, and c-Jun expression during subcultivation. c-Jun silencing inhibited cell proliferation and migration, while c-Jun overexpression enhanced proliferation but not migration. Compared with untransduced hUC-MSCs, local subcutaneous injection of c-Jun-overexpressing hUC-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased PDGFA and HGF levels in wound tissues. Conclusion c-Jun overexpression promoted hUC-MSC proliferation and migration in vitro and accelerated diabetic wound closure, reepithelization, and angiogenesis by hUC-MSCs in vivo. These beneficial effects of c-Jun overexpression in diabetic wound healing by hUC-MSCs were at least partially mediated by increased PDGFA and HGF levels in wound tissues.

Aryl piperazine suppresses cataractogenesis in a diabetic rat model via Nrf2/HO-1 signaling pathway

Purpose: To investigate the inhibitory potential of aryl piperazine on cataract formation in diabetic rats, and the underlying mechanism of action. Methods: Sprague-Dawley rats (7-week-old) were divided into 7 groups: control rats, untreated diabetic rats, and five aryl piperazine treatment groups given the drug at doses of 1, 2, 5, 10 and 15 mg/kg. Diabetes was induced in the rats via injection of streptozocin (STZ) in citrate buffer at a dose of 65 mg/kg. An ophthalmoscope was used to evaluate cataract formation, while GlucoLeader was used for the measurement of blood glucose level. Results: Aryl piperazine treatment significantly reduced blood glucose level from 6 to 12 weeks following administration of STZ, and prevented cataractogenesis in the diabetic rats (p < 0.05). Cataract score in the diabetic rats was also significantly decreased by aryl piperazine (p < 0.01). Aryl piperazine exposure reversed STZ-mediated decreases in antioxidant capacity (AOC) and glutathione (GSH) levels, enhanced glutathione peroxidase (GPX) activity and decreased malondialdehyde (MDA) levels in diabetic rats (p < 0.05). It suppressed the expressions of vascular endothelial growth factor (VEGF) and interleukin (IL)-1β in retinal tissues, while it upregulated the expressions of nuclear factor erythroid 2- related factor 2 (NRF2) and heme oxygenase (HO-1). Conclusion: Aryl piperazine suppresses cataractogenesis and reduces cataract score in diabetic rats by targeting oxidative stress. Moreover, in retinal tissues of diabetic rats, aryl piperazine activates Nrf2/mHO-1 signaling pathway. Thus, aryl piperazine has a potential for use in the prevention of cataracts.

Role of High-Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control.

Role of High-Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control.

Combination of weekly streptozocin and oral S-1 treatment for patients of unresectable or metastatic pancreatic neuroendocrine neoplasms.

Streptozocin (STZ) administration with or without other cytotoxic drugs remains a crucial chemotherapy for patients with advanced pancreatic neuroendocrine neoplasms (Pan-NENs). However, the therapeutic effects of combination treatment with weekly STZ and oral S-1 therapy (STS1) remain unknown. Therefore, the aim of this study was to evaluate the safety and clinical feasibility of STS1. Twenty of 243 Pan-NEN patients were included in this retrospective study, all of whom had received STS1 for unresectable or distant metastatic diseases from November 2015 to January 2019. The maximum tumor shrinkage rate, time course of the tumor shrinkage rate, prognosis (progression-free survival and overall survival), and adverse events were evaluated. The median age of the patients was 61.5years and the median tumor size was 35mm. The number of NET-G1, NET-G2, NET-G3, and NEC-G3 patients was 3, 13, 3, and 1, respectively. The median Ki-67 index and mitoses were 10.2% and 2/10 high-power fields, respectively. The overall objective response rate and disease control rate were 30% and 90%, respectively. The median maximum tumor reduction rate was 19%. The Ki-67 index and tumor size did not influence the tumor shrinkage rate. Progression-free survival after STS1 treatment was 19months with no significant difference between NET-G1/G2 and NET-G3/NEC-G3 patients (p = 0.4). There was one case each of grade 3/4 toxicity, including general fatigue, hyperglycemia, and renal dysfunction. No serious myelosuppressive events are manifested. STS1 treatment is an effective and safe therapeutic option for patients with advanced Pan-NEN.