Streptozotocin-induced Diabetes Mellitus Research Articles

Atractylenolide-I Alleviates Hyperglycemia-Induced Heart Developmental Malformations through Direct and Indirect Modulation of the STAT3 Pathway

BackgroundGestational diabetes could elevate the risk of congenital heart defects (CHD) in infants, and effective preventive and therapeutic medications are currently lacking. Atractylenolide-I (AT-I) is the active ingredient of Atractylodes Macrocephala Koidz (known as Baizhu in China), which is a traditional pregnancy-supporting Chinese herb. PurposeIn this study, we investigated the protective effect of AT-I on the development of CHD in embryos exposed to high glucose (HG). Study design and MethodsFirst, systematic review search results revealed associations between gestational diabetes mellitus (GDM) and cardiovascular malformations. Subsequently, a second systematic review indicated that heart malformations were consistently associated with oxidative stress and cell apoptosis. We assessed the cytotoxic impacts of Atractylenolide compounds (AT-I, AT-II, and AT-III) on H9c2 cells and chick embryos, determining an optimal concentration of AT-I for further investigation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR), and flow cytometry were utilized to delve into the mechanisms through which AT-I mitigates oxidative stress and apoptosis in cardiac cells. Molecular docking was employed to investigate whether AT-I exerts cardioprotective effects via the STAT3 pathway. Then, we developed a streptozotocin-induced diabetes mellitus (PGDM) mouse model to evaluate AT-I's protective efficacy in mammals. Finally, we explored how AT-I protects hyperglycemia-induced abnormal fetal heart development through microbiota analysis and untargeted metabolomics analysis. ResultsThe study showed the protective effect of AT-I on embryonic development using a chick embryo model which rescued the increase in the reactive oxygen species (ROS) and decrease in cell survival induced by HG. We also provided evidence suggesting that AT-I might directly interact with STAT3, inhibiting its phosphorylation. Further, in the PGDM mouse model, we observed that AT-I not only partially alleviated PGDM-related blood glucose issues and complications but also mitigated hyperglycemia-induced abnormal fetal heart development in pregnant mice. This effect is hypothesized to be mediated through alterations in gut microbiota composition. We proposed that dysregulation in microbiota metabolism could influence the downstream STAT3 signaling pathway via EGFR, consequently impacting cardiac development and formation. ConclusionsThis study marks the first documented instance of AT-I's effectiveness in reducing the risk of early cardiac developmental anomalies in fetuses affected by gestational diabetes. AT-I achieves this by inhibiting the STAT3 pathway activated by ROS during gestational diabetes, significantly reducing the risk of fetal cardiac abnormalities. Notably, AT-I also indirectly safeguards normal fetal cardiac development by influencing the maternal gut microbiota and suppressing the EGFR/STAT3 pathway.

Structural characterization of squash polysaccharide and its effect on STZ-induced diabetes mellitus model in MIN6 cells

A novel natural water-soluble acidic polysaccharide (PWESP-3) was isolated from squash with a molecular mass of 140.519 kDa, which was composed of arabinose (Ara, 35.30 mol%), galactose (Gal, 61.20 mol%), glucose (Glc, 1.80 mol%), and Mannuronic acid (ManA, 1.70 mol%) and contained Araf-(1→, →3)-Araf-(1→, →5)-Araf-(1→, Glcp-(1→, Galp-(1→, →3,5)-Araf-(1→, →2)-Glcp-(1→, →2)-Manp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →3)-Galp-(1→, →6)-Galp-(1→, →3,4)-Galp-(1→, →4,6)-Galp-(1→ residues in the backbone. Moreover, the structure of PWESP-3 was identified by NMR spectra. The branch chain was connected to the main chain by the O-3 and O-4 atom of Gal. In addition, the effect of PWESP-3 on STZ-induced type I diabetes mellitus model in MIN6 cells was investigated. The results showed that PWESP-3 can increase the viability and insulin secretion of MIN6 cells and reduce the oxidative stress caused by ROS and NO. Meanwhile, PWESP-3 can also reduce the content of ATP, Ca2+, mitochondrial membrane potential and Caspase-3 activity in MIN6 cells. Furthermore, treatment with PWESP-3 can prevent single or double stranded DNA breaking to form DNA fragments and improve DNA damage in MIN6 cells, thereby avoiding apoptosis. Therefore, the above data highlight that PWESP-3 can improve the function of insulin secretion in STZ-induced MIN6 cells in vitro and can be used as an alternative food supplement to diabetes drugs.

Phenotypes of streptozotocin-induced gestational diabetes mellitus in mice.

Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.

Effect of Carnosine on Oxidative Damage to the Kidneys in Experinental Diabetes Mellitus

The article presents the results of a study into the effect of carnosine on oxidative damage to the kidneys in experimental diabetes mellitus. The experiment was carried out using two groups of Wistar rats: control (n=8) and experimental (n=11). In both groups, streptozotocin-induced diabetes mellitus was simulated for eight weeks. Experimental animals were intragastrically injected with carnosine (15 mg/kg) from weeks 4 to 8. The concentration of glucose, protein and creatinine excretion in urine were determined. At the end of eight weeks, the kidneys were removed from the rats to determine the indicators of oxidative stress severity (concentration of thiobarbiturate-reactive products, total antioxidant activity, activity of catalase, superoxide dismutase, glutathione peroxidase) and to conduct morphometry of the size of the renal glomeruli, the area of the vascular bed, capillaries and mesangium in the glomeruli, the number of podocytes. A comparison with the control showed the use of carnosine led to a 1.5-fold decrease in the concentration of thiobarbiturate-reactive products (p<0.001), a 2.2-fold increase in the total antioxidant activity (p<0.001), and a 1.2-fold increase in catalase activity (p=0.039). The area of the renal glomeruli and the mesangium in this group decreased by 1.6 times (p<0.001 and p=0.04, respectively). The total area of blood flow increased by 2.4 times (p<0.001), the area of one capillary, and the number of podocytes in the glomerulus increased by 1.9 times (p<0.001 and p=0.001). A 3.5-fold decrease in protein concentration in urine was also noted (p=0.007). Therefore, inhibition of the formation of advanced glycation end products by carnosine in experimental diabetes mellitus attenuates oxidative damage to the kidneys. This is evidenced by a decrease in proteinuria, an increase in the number of podocytes, a decrease in the area of the renal glomeruli, and an improvement in the condition of the glomerular vascular system.

A Polyherbal extract treats Streptozotocin induced Diabetes mellitus: Pharmacognostic study, HPLC analysis and in vivo antidiabetic activity

The plants used in study have been used traditionally for various purposes skin problems, diabetes, astringent, anti-inflammatory, antioxidant, hepatoprotective activities, anthelmintic, antipyretic, antidysentric, anti-hyperlipidemic, anticancer properties. The present study involves the evaluation of pharmacognostic parameters of the four herbal drugs (Azadirachta indica leaves, Pterocarpus marsupium heartwood, Picrorhiza kurroa rhizomes, and Withania coagulans berries and fruit coat), High performance Liquid chromatography (HPLC) as well as antidiabetic activity of polyherbal extract. The qualitative as well as quantitative analysis was done. The drug was given to Streptozotocin induced diabetic rats in doses 250 mg/kg and 500 mg/kg body weight for 21 days. In HPLC analysis it was found that major component in all the extracts was beta carotene along with hesperidin, tannic acid, catechin, ferulic acid, caffeic acid along with other polyphenolic components responsible for the antioxidant activity as well as antidiabetic activity of polyherbal extract. Rats were found to show an increase in body weight, improved blood sugar levels and hemoglobin. The liver glycogen, total proteins, serum lipid profile were restored back to normal range after using the polyherbal extract in diabetic rats. The histopathological study also shows an improvement in diabetic rats at cellular level. The results were found to be dose dependent.

Uncovering the Mechanisms of Cinnamic Acid Treating Diabetic Nephropathy Based on Network Pharmacology, Molecular Docking, and Experimental Validation.

Cinnamic acid (Cinn) is a phenolic acid of Cinnamomum cassia (L.) J. Presl. that can ameliorate diabetic nephropathy (DN). However, comprehensive therapeutic targets and underlying mechanisms for Cinn against DN are limited. In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy. The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn. Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice. This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.

Immunomodulation of streptozotocin induced Type 1 diabetes mellitus in mouse model by Macrophage migration inhibitory factor-2 (MIF-2) homologue of human lymphatic filarial parasite, Wuchereria bancrofti

Helminth parasites modulate the host immune system to ensure a long-lasting asymptomatic form of infection generally, mediated by the secretion of immunomodulatory molecules and one such molecule is a homologue of human host cytokine, Macrophage migratory Inhibitory Factor (hMIF). In this study, we sought to understand the role of homologue of hMIF from the lymphatic filarial parasite, Wuchereria bancrofti (Wba-MIF2), in the immunomodulation of the Streptozotocin (STZ)-induced Type1 Diabetes Mellitus (T1DM) animal model. Full-length recombinant Wba-MIF2 was expressed and found to have both oxidoreductase and tautomerase activities. Wba-MIF2 recombinant protein was treated to STZ induced T1DM animals, and after 5 weeks pro-inflammatory (IL-1, IL-2, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and gene expressions were determined in sera samples and spleen respectively. Pro-inflammatory and anti-inflammatory cytokine levels were significantly (p<0.05) up-regulated and down-regulated respectively, in the STZ-T1DM animals, as compared to treated groups. Histopathology showed macrophage infiltration and greater damage of islets of beta cells in the pancreatic tissue of STZ-T1DM animals, than Wba-MIF2 treated STZ-T1DM animals. The present study clearly showed the potential of Wba-MIF2 as an immunomodulatory molecule, which could modulate the host immune system in the STZ-T1DM mice model from a pro-inflammatory to anti-inflammatory milieu.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study

BackgroundMicrovascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique.MethodsTwelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function.ResultsWith the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = − 0.353, P = 0.022), LV remodeling index (r = − 0.312, P = 0.033), fasting blood glucose (r = − 0.313, P = 0.043), and HbA1c (r = − 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration.ConclusionsMyocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Potency of &lt;i&gt;Clitoria ternatea&lt;/i&gt; L. Ethanol Extract Against IFNγ and GLUT4 Protein in Type 2 Diabetes Mellitus Rat Model

Diabetes Mellitus (DM) is a chronic disease caused by genetics, lifestyle, and immunology. Type 2 DM is caused by resistanceto insulin, which causes blood sugar to not be stored in glycogen. Clitoria ternatea L. (Fabaceae) flower contains a lot ofanthocyanins and has long been used in various traditional medicines. They are believed to treat fever, inflammation, anddiabetes. Anthocyanins have antidiabetic, anticancer, anti-inflammatory, and anticancer properties. This study aimed toevaluate anti-DM of Clitoria ternatea L. flower extract (CTE) in DM model rats with parameters such as liver weight ratio,IFNγ, and GLUT4 protein expression in pancreas and femoral muscle. Rats with a streptozotocin-induced (STZ) DM modelwere used to test the effects of oral administration of CTE at doses of 200, 400, and 800 mg/kg BW, glybenclamide (0.45mg/kg BW), and simvastatin (0.9 mg/kg BW). After blood sugar levels were &gt;200 mg/dL, the rats were given various dosesof CTE and tested for protein expression of IFNγ and GLUT4 in femoral muscle by immunohistochemistry (IHC) method.Data analysis used ANOVA and continued with Tukey’s post hoc test. Results showed that CTE could increase liver ratiowhile decreasing IFNγ activation at CTE 400 mg/kg BW and upregulating GLUT4 at 400 mg/kg BW. CTE has an anti-DM activity potential for diabetes mellitus treatment due to its anthocyanin content.

Toxicological Assessment and Anti-diabetic Effects of Combined Extract of Chirata, Fenugreek and Sesame on Regulating TNF-α, TGF-β and Oxidative Stress in Streptozotocin Induced Diabetic Rats.

Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum are used as traditional medicines to treat diabetes mellitus. A collection of metabolic illnesses known as diabetes mellitus (DM) involves chronic hyperglycemia caused by flaws in insulin secretion, function, or both. Innate immunity and inflammation both play important roles in the etiology of diabetes-related microvascular problems. This study aims to examine the anti-diabetic effects and the acute toxicity of combined extract (1:1:1) of Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum. To address the demand for higher effectiveness and safety, the current effort aims to construct anti-diabetic preparations containing methanolic extract from herbal medications. The OECD 423 method was used to investigate acute toxicity in rats. Rats were used as test subjects, and rats were given a 35 mg/kg BW injection of streptozotocin to develop diabetes. The diabetic control group was given Glibenclamide 25 mg/kg BW, while the experimental group's diabetic rats received 125 mg/kg BW and 250 mg/kg BW of a combined methanolic extract of all plants. Among the measurements looked at were acute oral toxicity, behavioral changes, body weight, serum glucose levels, lipid profiles, oxidative stress, renal function tests, and inflammatory mediators. All the rat groups' histopathologies of the kidney, liver, and stomach were compared. The data were evaluated using analysis of variance, and a post hoc test was then carried out. The combined extracts' medium lethal doses (LD50) were higher than 2000 mg/kg, indicating that they are not poisonous under the conditions that can be observed. Streptozotocin-induced diabetic rats' elevated blood glucose was found to be considerably lower (p 0.01) in the treated group of rats. In the treated group of rats, it was discovered that the damage and disarray in the cells typical of Streptozotocin-induced DM had been repaired. The treated group of rats returned to normal levels of the lipid profile, hyperglycemia, decreased serum protein and liver glycogen, increased liver function, and kidney function markers seen in the rats of the DM control group. The evaluated combined methanolic extract can be considered safe for use in rats. Combining methanolic extract from all selected medicinal plants (Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum) has a potential anti-diabetic effect and can be safely developed as an alternative medicine.

Age characteristics of myocardial blood supply in comorbid pathology

Understanding the age-related changes in myocardial blood supply under conditions of diabetes mellitus and stress will help reveal the pathway of diabetic cardiomyopathy, considering the age aspect. Therefore, the aim of our work is to investigate the age-related morpho-functional changes in the hemomicrocirculatory bed (HMB) of the myocardium in rats with experimental streptozotocin-induced diabetes mellitus (SDM) under conditions of chronic immobilization stress (CIS). The study used heart fragments and blood from 56 2-month-old and 6-month-old male white rats, which were divided into 3 groups: 1 group with comorbid pathology, including modeled SDM and CIS, 2 group with SDM, and 3 – control group. The material was collected 14th and 56th days from the start of the experiment. According to our findings, hyperglycemia, and stress on the 14th day of the experiment lead to spasm of the arterioles of the HMB and a significant deterioration in their permeability, as evidenced by a likely increase in the Vongenwort index in the arterioles. On the 56th days, in the experimental groups of 6-month-old rats, vacuolar dystrophy and coagulation necrosis of endotheliocytes and myocytes, focal destruction of capillary walls, thickening, and proliferation of their basement membrane, pronounced micro- and macroclasmatic changes, and capillarosclerosis are observed. In contrast, 2-month-old rats alongside destructive changes in HMB vessels show phenomena of neovascularization. Thus, SCD leads to the development of diabetic microangiopathy in the vessels of the myocardium of rats of different age groups. In animals with comorbid pathology, damage of HMB vessels are more pronounced on the 56th day of observation and is manifested by: destruction of capillary walls, capillarosclerosis. In 2-month-old rats, alongside destructively changed capillaries, we found to former new vessels with a characteristic ultrastructure. Keywords: heart, heart failure, diabetic cardiomyopathy, diabetes mellitus, cardiovascular diseases, hemomicrocirculatory bed.

Role of serotonin on pituitary-thyroid functions and antioxidants in diabetic male rats

Diabetes mellitus causes an increase in oxidative stress. Serotonin is a hormone its level in circulation reduced in diabetes; recently, it has been found to possess antioxidant qualities. The purpose of the study was to look at the impact of diabetes on pituitary-thyroid functioning, and serotonin role in modulating these effects in a streptozotocin-induced diabetes mellitus rat model. The thirty-tow healthy male rats with a body weight of 180-200 gm were split equally into 4 groups, group [1[: control, group [2]: Serotonin, group [3]: diabetic, and group [4]: Serotonin-diabetic. The rats were weighed and serum levels of glucose, insulin, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, serotonin, thyroid stimulating hormone, thyroxine, and triiodothyronine were measured. Our results presented that there was a significant increase in T3, T4, glucose, and MDA in the diabetic group compared to the control, while a significant decrease in T3, and T4, glucose, and MDA in the Serotonin with diabetic group compared to diabetic group. Furthermore, a significant decrease in TSH, serotonin, insulin and GPX, CAT, and SOD antioxidants in the diabetic group compared to control, while a significant increase in serum TSH, serotonin, insulin and CAT, GPX and SOD antioxidants in the Serotonin+diabetic group compared to diabetic group as well as a significant increase in serum insulin in the Serotonin group compared to all other groups. Serotonin plays a protective role against diabetes-induced and pituitary-thyroid disorder caused by diabetes which might be because of its antioxidant qualities and ability to maintain glucose and insulin balance.  

Treatment of a non-healing oral wound in diabetic-induced rats

Aim: Non-healing wounds are one of the most substantial and difficult problems to treat. Wound healing involves a sequence of complex biological processes, but often the oral cavity microbiota adversely affects healing and forms a chronic non-healing wound. Methods: In this study, a biologically active membrane (BAM) is present, consisting of decellularized human amniotic membrane and bone marrow stem cells (BMSCs). The efficacy of BAM was evaluated in a model of non-healing oral wounds in rats with streptozotocin (STZ)-induced diabetes mellitus. Results: Studies have shown that BAM enhanced the healing of chronic oral wounds in animals with induced diabetes mellitus, reduced scarring, and reduced risk of infection. Paracrine freeze-dried BMSCs stimulated angiogenesis and improved wound conditions. Conclusions: BMSCs may lower glucose levels in rats with STZ-induced diabetes mellitus and improve the healing process of chronic diseases. However, more studies are needed to study the paracrine factors of BMSCs and their role in the treatment of non-healing wounds.

Diabetes-correcting and antioxidant effects of grape pomace extract rich in natural complex of polyphenols

Background. The positive health effects of polyphenols have led to an increased scientific interest in these natural compounds over the past decade. Many studies confirm the effectiveness of polyphenols as additional therapy in diabetes, especially due to the sugar-lowering effect of polyphenols. The aim of the research was to investigate the morphological and functional state of peripheral blood erythrocytes and the indices of oxidative stress in the liver of rats with experimental diabetes and after the administration of grape pomace extract rich in natural complex of polyphenols. Materials and Methods. We obtained grape pomace extract, which contains a variety of polyphenolic compounds. Rats of the following groups were used in the experiments: control animals, animals treated with grape pomace extract rich in natural complex of polyphenols for 14 days, animals with streptozotocin-induced diabetes mellitus, and animals with streptozotocin-induced diabetes mellitus treated with grape pomace extract rich in natural complex of polyphenols for 14 days. The number of erythrocytes and reticulocytes, the concentration of hemoglobin and glycated hemoglobin were determined in the peripheral blood of rats. The activities of catalase, superoxide dismutase and the content of thiobarbituric acid-reactive substance and carbonyl groups of proteins were determined in the liver tissues of rats. Results. The study has shown an increase in the number of erythrocytes and the level of hemoglobin, a decrease in the level of glycated hemoglobin and the number of reticulocytes in the peripheral blood of rats after administration of grape pomace extract rich in natural complex of polyphenols to rats with experimental diabetes. A decrease in the content of thiobarbituric acid-reactive substance and the content of carbonyl groups of proteins of neutral and basic character and an increase in the activity of catalase and superoxide dismutase in liver tissues were found under the same conditions. Conclusions. The results indicate that the extract of the natural complex of polyphenols is capable of correcting the morphological and functional state of erythrocytes, as well as improving the activity of antioxidant enzymes and the content of marker molecules of oxidative stress in hepatocytes of rats under experimental diabetes mellitus.

Influence of rosiridin on streptozotocin-induced diabetes in rodents through endogenous antioxidants-inflammatory cytokines pathway and molecular docking study

The research was undertaken to assess the antidiabetic activity of rosiridin in the streptozotocin (STZ)-induced diabetic model. Type 2 diabetes mellitus was elicited chemically in experimental animals using STZ (60 mg/kg, i.p.). Experimental rats were arbitrarily allocated to normal control, rosiridin perse, diabetic control, and STZ + rosiridin groups. After the confirmation of diabetes, rosiridin (10 mg/kg) was given orally to the experimental animals for 30 days. Various anti-diabetic (blood glucose, insulin), hypolipidemic, anti-inflammatory (Nuclear factor kappa B, tumour necrosis factor-α, interleukin beta (IL-1β), and IL-6), antioxidant (and malondialdehyde level, hepatic function and others markers (ALT, AST, adiponectin, and FNDC5) and histopathological indices of injury were evaluated. In addition, the rosinidin was docked into the active site of NF-Kβ (1SVC), FNDC5 (4LSD) and adiponectin (5LXG) proteins with AutoDock tools. MD simulations were carried out for the complexes of rosiridin with NF-Kβ, myokine and human adiponectin receptor 1. Rosiridin treatment restored the biochemical parameters and preserved the histopathological building of the pancreas as compared to the diabetic rats. Histopathological analysis of the pancreas confirmed that rosiridin antidiabetic efficacy in the STZ-induced diabetes mellitus model. The 5LXG_rosinidin showed favourable affinity with the best binding energies at −7.534 kcal/mol. MD simulations were carried out for the complexes of rosiridin with NF-Kβ, myokine and human adiponectin receptor 1, the complex of myokine and rosiridin exhibited the most stable complex. Rosiridin may exhibit considerable anti-diabetic activity in the STZ-induced diabetes mellitus model. Communicated by Ramaswamy H. Sarma

Effect of Boric Acid on Metabolic Peptides and Some Biochemical Parameters in Experimental Diabetic Rats.

Boron (B) is an element that has recently been wondered and researched in many fields, especially due to its effects on energy metabolism. The aim of this study is to evaluate the effect of boric acid (BA) on newly discovered energy metabolism peptides that have not been studied before. In this study, the effects of 15 mg/kg of BA were evaluated in 24 Wistar rats. Groups were named as control group, 15 mg/kg BA group, streptozotocin (STZ)-induced experimental diabetic group, and STZ-induced experimental diabetic + 15 mg/kg BA administered group (STZ+15 mg/kg BA). Serum asprosin, nesfatin-1, preptin, insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), and glucose analyses were performed. In this study, the increase in glucose, TG, TC, LDL-C levels, and AST, ALT activities in STZ-induced groups were reduced with BA administration. While HDL-C level significantly decreased in the STZ group, the level approached the control group values after BA administration (p<0.001). As for peptides, although there was a statistically significant increase after 15 mg/kg BA administration, these levels did not approach the control group values (p<0.001). According to the findings, STZ-induced diabetes mellitus and the biochemical processes that develop accordingly change correlatively. This study showed that BA is effective in energy metabolism.

Anti-Diabetic Effects of Pomegranate Peel Extract and L-Carnitine on Streptozotocin Induced Diabetes In Rats

Type 2 diabetes mellitus is a far reaching ongoing metabolic problem portrayed by hyperglycemia and related with a few intricacies like hyperlipidemia. The current study aimed to study the anti-diabetic efficacy of pomegranate peel extract and L-carnitine on streptozotocin-induced diabetes mellitus in rats. A total of 70 male rats were divided into 7 groups (normal rats treated with the pomegranate peel extract and L-carnitine; rats given a high-fat diet to cause hyperlipidemia, this rats given low-dose intraperitoneal streptozotocin injections to cause type II diabetes; diabetic rats given PPE and L-carnitine orally every day for 12 weeks. Measurements of body mass, blood sugar, lipid profile and antioxidant enzyme activity were made.Results: The treatment group that received PPE + L-carnitine showed a significant decrease in weight, blood glucose, cholesterol, triglycerides and low-density lipoprotein were significantly reduced, while high-density lipoprotein levels were significantly increased. Superoxide dismutase levels were increased, catalase and Nuclear Factor Erythroid-derived 2 (Nfe2) in diabetic rats treated with PPE and L-carnitine, while Malondialdehyde levels decreased significantly. According to the results of the study, PPE and L-carnitine had significant anti-hyperglycemic, hypolipidemic, and antioxidant benefits after 12 weeks of treatment in streptozotocin-induced diabetic rats.

Morphologic characteristic of rat myocardium in comorbid pathology

Diabetic cardiomyopathy is a serious complication of diabetes mellitus (DM). Aim. Therefore, we aimed to study myocardial changes in adult rats with streptozotocin (STZ)-induced DM exposed to chronic immobilization stress (CIS). Materials and methods. A total of 26 adult albino male rats weighing 180–200 g were examined. All the animals were divided into three groups: Group I included 10 rats with STZ-induced DM exposed to CIS; Group II comprised 10 rats with STZ-induced DM; Group III included 6 intact animals. The samples were collected on the 14th and 56th days of the experiment. Histological, histochemical, electron microscopy, and biochemical methods were used. Results. On the 14th day of the experiment, in Group I and Group II, increased blood flow was observed in the capillaries, venules, and veins, while an arteriolar spasm in the microcirculation was found. In addition, cardiomyocyte surface area in different myocardial regions reduced due to low glycogen content as confirmed by histochemical and ultrastructural studies. On the 56th day of the experiment, in Group I and Group II, hyperemia occurred due to red blood cell aggregation and microthrombi. The surface area of all microcirculatory vessels increased as compared to that of intact animals, as evidenced by an increase in their wall surface area leading to an increase in their wall-to-lumen ratio. Such morphometric changes in the microcirculatory vessels were indicative of decreased vascular permeability and impaired myocardial blood flow. At the histological level, in Group I and Group II, focal cardiomyocyte lysis, moderate to diffuse stromal edema, lymphohistiocytic infiltration were seen. Such changes pointed to sterile inflammation, probably due to myocardial infraction secondary to diabetic microangiopathy. In cardiomyocytes, karyolysis, vacuolar degeneration, apical ballooning, subsarcolemmic edema, fibrosis and lysis of myofibrils, colliquative necrosis were observed. Conclusions. STZ-induced DM and stress resulted in pronounced destructive changes in the myocardium of rats, including interstitial edema, focal cardiosclerosis, myolysis. Such changes occurred on the background developing diabetic microangiopathy. The most pronounced myocardial changes were recorded in animals with a comorbidity.

Targeted deletion of von-Hippel-Lindau in the proximal tubule conditions the kidney against early diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Glomerular hyperfiltration and albuminuria subject the proximal tubule (PT) to a subsequent elevation of workload, growth, and hypoxia. Hypoxia plays an ambiguous role in the development and progression of DKD and shall be clarified in our study. PT-von-Hippel-Lindau (Vhl)-deleted mouse model in combination with streptozotocin (STZ)-induced type I diabetes mellitus (DM) was phenotyped. In contrary to PT-Vhl-deleted STZ-induced type 1 DM mice, proteinuria and glomerular hyperfiltration occurred in diabetic control mice the latter due to higher nitric oxide synthase 1 and sodium and glucose transporter expression. PT Vhl deletion and DKD share common alterations in gene expression profiles, including glomerular and tubular morphology, and tubular transport and metabolism. Compared to diabetic control mice, the most significantly altered in PT Vhl-deleted STZ-induced type 1 DM mice were Ldc-1, regulating cellular oxygen consumption rate, and Zbtb16, inhibiting autophagy. Alignment of altered genes in heat maps uncovered that Vhl deletion prior to STZ-induced DM preconditioned the kidney against DKD. HIF-1α stabilization leading to histone modification and chromatin remodeling resets most genes altered upon DKD towards the control level. These data demonstrate that PT HIF-1α stabilization is a hallmark of early DKD and that targeting hypoxia prior to the onset of type 1 DM normalizes renal cell homeostasis and prevents DKD development.

Brassinin Exhibits Anti-Diabetic Activity against Streptozotocin-induced Diabetes Mellitus in Experimental Rats

Brassinin Exhibits Anti-Diabetic Activity against Streptozotocin-induced Diabetes Mellitus in Experimental Rats