Effects of Timolol Treatment on Pancreatic Antioxidant Enzymes in Streptozotocin-induced Diabetic Rats: An Experimental and Computational Study.
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ABSTRACT:
SUBMITTER: Ulusu NN
PROVIDER: S-EPMC6534949 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Project description:Diabetes mellitus (DM) causes not only hyperglycemia but oxidative stress, resulting mainly enhanced production of mitochondrial reactive oxygen species (ROS). Hyperbaric oxygen (HBO) treatments are applied various diseases including diabetic patients with unhealing foot ulcers, however, and also increases the formation of ROS. Recently, it has been reported that oxidative stress worsens many pathological conditions including DM and obesity suggesting possible changes in regulation of genes associated with the oxidative stress, however, effects of HBO which could induce ROS on the gene expressions of oxidative stress parameters in DM animals are unknown. The purpose of this study is to investigate the effect of HBO exposure on the gene expression of three important antioxidant enzymes, cytosolic superoxide dismutase (Cu-Zn SOD), cytosolic glutathione peroxidase (GPx-1), and catalase (CAT) in DM rats, respectively. We used streptozotocin-induced DM model rats and examined both mRNA expressions and the activities of these antioxidant enzymes in the liver, skeletal muscle, and pancreas. The mRNA expressions of Cu-Zn SOD and CAT decreased significantly (p < 0.001), and GPx increased significantly (p < 0.001) in all the studied organs of DM rats under HBO exposure compared to those from DM-induced rats not exposed to HBO. Similarly, activities of these three enzymes changed in accordance with the mRNA levels. These results suggested that DM induction and HBO exposure might synergistically affect antioxidant enzymes, resulting increase of oxidative stress state. Thus, HBO exposure seems to be an excellent model system for investigating oxidative stress.
| S-EPMC2809998 | biostudies-literature
Project description:Oxidative stress attributes a crucial role in chronic complication of diabetes. The aim of this study was to determine the most effective part of pomegranate on oxidative stress markers and antioxidant enzyme activities against streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Male Sprague-Dawley rats were randomly divided into six groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p), 15 min after the i.p administration of NA. Diabetic rats showed significant increase in plasma glucose level, and the significant decrease in plasma insulin level. The activities of antioxidant enzymes such as total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) reduced while the levels of biomarkers of oxidative stress such as gamma-glutamyle transferase (GGT), and malondialdehyde (MDA) increased in diabetic control rats as compared to normal control rats. Oral treatment with pomegranate seed-juice for 21 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were supported by histopathological study. These results revealed that pomegranate has potential protective effect against oxidative stress induced diabetic rats.
| S-EPMC5598111 | biostudies-literature
Project description:Background and purposeRetinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats.Experimental approachRats were injected with a single i.p. injection of STZ (60 mg·kg⁻¹) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg⁻¹·d⁻¹ of 0.28 mol·L⁻¹ NaHS, a donor of H₂S) for 14 weeks.Key resultsTreatment with H₂S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H₂S enhanced H₂S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H₂S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H₂S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation.Conclusions and implicationsTreatment with H₂S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.
| S-EPMC3682709 | biostudies-literature
Project description:Patients with diabetes often have difficult-to-heal wounds. Spinacia oleracea extract comprises anti-inflammatory and anti-oxidative compounds; this research, therefore, studied the impact of Spinacia oleracea extracts on ulcer regeneration. This study was conducted on 72 adult Wistar rats (200 [Formula: see text] 20 g). They were randomly divided into six groups of twelve. A: Diabetic group receiving normal saline. B: Non-diabetic group receiving normal saline. C: Diabetic group receiving spinach aqueous extract. D: Diabetic group receiving spinach alcoholic extract. E: preventive group that received aqueous extract for 2 months. F: preventive group that received alcoholic extract for 2 months. Ulcer regeneration, vascular endothelium growth factor, blood sugar, and weight changes were measured on days 3, 7, 14, 21, and 30. Macroscopic investigation of the wounds non-diabetic control group, diabetic group, as well as spinach aqueous and alcoholic extract groups, were compared and there were significant changes (P < 0.05). Pathologic examination in the spinach aqueous and alcoholic extract groups, and nondiabetic group than in the diabetic group revealed significant advances (P < 0.05). On the third and seventh days, Vascular endothelium growth factor detected significant differences between groups (P < 0.05). Results indicate that, in regenerating diabetic ulcers, Spinacia oleracea may be effective. It influences the ulcer structure and speed.
| S-EPMC10495437 | biostudies-literature
Project description:Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ?+?SPR) or saline (STZ?+?NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-?1, TNF-?, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ?+?NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.
| S-EPMC6204188 | biostudies-literature
Project description:Diabetic nephropathy (DN) is a major complication of diabetes and is caused by an imbalance in the expression of certain genes that activate or inhibit vital cellular functions of kidney. Despite several recent advances, the pathogenesis of DN remains far from clear, suggesting the need to carry out studies identifying molecular aspects, such as gene expression, that could play a key role in the development of DN. There are several techniques to analyze transcriptome in living organisms. In this study, the suppression subtractive hybridization (SSH) method was used to generate up- and down-regulated subtracted cDNA libraries in the kidney of streptozotocin (STZ)-induced diabetic rats. Northern-blot analysis was used to confirm differential expression ratios from the obtained SSH clones to identify genes related to DN. 400 unique SSH clones were randomly chosen from the two subtraction libraries (200 of each) and verified as differentially expressed. According to blast screening and functional annotation, 20.2% and 20.9% of genes were related to metabolism proteins, 9% and 3.6% to transporters and channels, 16% and 6.3% to transcription factors, 19% and 17.2% to hypothetical proteins, and finally 24.1 and 17.2% to unknown genes, from the down- and up-regulated libraries, respectively. The down- and up-regulated cDNA libraries differentially expressed in the kidney of STZ diabetic rats have been successfully constructed and some identified genes could be highly important in DN.
| S-EPMC3257079 | biostudies-literature
Project description:Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as "aragh gazaneh". In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats.A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups.The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered.UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells.
| S-EPMC5936849 | biostudies-other
Project description:This study is aimed at comparing the antidiabetic and antioxidant potential of fenugreek and buckthorn which are commonly used in modulating diabetes in the Middle East. In this study, the antioxidant and antidiabetic activity of the aqueous extracts of the leaf and seed of fenugreek and buckthorn was tested in streptozotocin-induced diabetic male rats fed with a fat-rich diet for 8 weeks. Thirty-six male albino rats were divided into 6 groups (n = 6); the 1st group was the negative control. Diabetes was induced in the other 30 rats using streptozotocin, which were then divided into 5 groups; the 2nd was the untreated positive diabetic group, the 3rd was treated with fenugreek leaf aqueous extract, the 4th was treated with the fenugreek seed aqueous extract, the 5th was treated with buckthorn leaf aqueous extract, and the 6th was treated with buckthorn seed aqueous extract. The positive control group showed an increase in blood sugar, glycated hemoglobin, liver function enzymes, lactate dehydrogenase, kidney indices, total cholesterol, triglycerides, low- and very-low-density lipoprotein, immunoglobulins, and lipid peroxidation and a decrease in high-density lipoprotein, albumin, and antioxidant activity. The histology of the liver and testes showed severe histopathological alterations. Rats of groups 4-6 that were treated with the aqueous extract of the leaf and seed extract of fenugreek and buckthorn showed improvement of all biochemical and histopathological parameters. The seed extract of fenugreek and buckthorn showed more antioxidant activity than their leaves.
| S-EPMC8420976 | biostudies-literature
Project description:BACKGROUND:Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. METHODOLOGY/PRINCIPAL FINDINGS:Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. CONCLUSIONS:Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction.
| S-EPMC3145674 | biostudies-literature
Project description:BACKGROUND:The fruit of Elaeagnus umbellata has high medicinal values and is an excellent source of phytochemicals. This study was aimed to evaluate the antioxidant, enzyme inhibitory and antidiabetic potential of Elaeagnus umbellata. METHODS:The antioxidant potential of the crude extract and subfractions of E. umbellata fruit were determined using DPPH (2, 20-diphenyl-1-picrylhydrazyl) and ABTS (2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The enzyme inhibitory potentials of extracts against ?-amylase and ?-glucosidase enzymes were also determined. The in vivo anti-hyperglycemic effects of the extract in STZ-induced type 2 diabetes were determined using Sprague Dawley adult rats. HPLC system (Agilent 1260) was used for the identification of bioactive compounds present in extracts. Molecular docking was used to identify and compare the interaction between the compounds (active constituents) and standard inhibitor acarbose with the ?-amylase and ?-glucosidase active sites. RESULTS:The chloroform, ethyl acetate, and butanol fractions showed significant antioxidant potential with IC50 values of 40, 45 and 60??g/mL against DPPH and 57, 70 and 120??g/mL against ABTS free radicals respectively. The chloroform and ethyl acetate were highly active against ?-amylase and ?-glucosidase (IC50 values 58 and 200??g/ml against ?-amylase 60 and 140??g/ml against ?-glucosidase. The crude extract, chloroform, and ethyl acetate fractions were more potent in controlling the hyperglycemia in STZ-induced type 2 diabetes in rats and considerable reduction of glucose level was observed compared to the non-treated group. Furthermore, the extracts were also found useful in controlling the secondary complications associated with type 2 diabetes mellitus which was evident from the observed substantial reduction in the blood level of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, total cholesterol, low-density lipoproteins, and triglycerides. The molecular docking approach indicated the favorable inhibitory interaction between the docked compounds and the active sites of the ?-amylase and ?-glucosidase. All docked compounds occupied the same binding site as occupied by acarbose. CONCLUSION:It was concluded that E. umbellata can be used in the treatment of type 2 diabetes and oxidative stress. The extracts were also found to be effective in relieving the secondary complications associated with type 2 diabetes.
| S-EPMC6293591 | biostudies-literature