Oxidative Stress In Diabetes Research Articles

Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.

Diabetic complications pose a significant threat to life and have a negative impact on quality of life in individuals with diabetes. Among the various factors contributing to the development of these complications, endothelial dysfunction plays a key role. The main mechanism underlying endothelial dysfunction in diabetes is oxidative stress, which adversely affects the production and availability of nitric oxide (NO). Flavonoids, a group of phenolic compounds found in vegetables, fruits, and fungi, exhibit strong antioxidant and anti-inflammatory properties. Several studies have provided evidence to suggest that flavonoids have a protective effect on diabetic complications. This review focuses on the imbalance between reactive oxygen species and the antioxidant system, as well as the changes in endothelial factors in diabetes. Furthermore, we summarize the protective mechanisms of flavonoids and their derivatives on endothelial dysfunction in diabetes by alleviating oxidative stress and modulating other signaling pathways. Although several studies underline the positive influence of flavonoids and their derivatives on endothelial dysfunction induced by oxidative stress in diabetes, numerous aspects still require clarification, such as optimal consumption levels, bioavailability, and side effects. Consequently, further investigations are necessary to enhance our understanding of the therapeutic potential of flavonoids and their derivatives in the treatment of diabetic complications.

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

Background. In diabetes mellitus (DM), analysis of changes in the biochemical profile of erythrocytes is the important stage of complex scientific research to clarify the mechanism of action of medicinal products based on plant raw materials. The fruits of Cornus mas L. are widely known. The biologically active compounds of these fruits show multiple biological effects. However, the effect of the fruit extracts of cornelian cherry on the functional state of erythrocytes in diabetes has not been sufficiently studied. The high glucose concentration in erythrocytes induces various structural and functional changes, which lead to numerous disturbances in their metabolism. Glucose transported into erythrocytes by facilitated diffusion via GLUT2 undergoes catabolic breakdown in anaerobic glycolysis (90 % of all glucose) and pentose phosphate pathway (the rest 10 %). ATP and reduced coenzymes of NADH + H+ and NADPH + H+ formed due to metabolism participate in maintaining the structure of hemoglobin. Enzymes of the antioxidant defense system, which prevent hemoglobin oxidation into methemoglobin, are especially important. Hyperglycemia and the development of oxidative stress in diabetes are the cause of a decrease in the activity of antioxidant enzymes and the accumulation of ligand forms of hemoglobin (HbCO2, MetHb, HbA1c). Therefore, the work aimed to investigate the effect of extracts of red and yellow fruits of Cornus mas L. on the content of end products of the glycolytic breakdown of glucose in erythrocytes and biochemical markers of the antioxidant status of these blood cells in rats with streptozotocin-induced diabetes. Materials and Methods. DM 1 type in animals was induced by intraperitoneal injection of streptozotocin. Experiments were performed on male Wistar rats, who, from the 10th day after diabetes induction, were administered per os extracts of red and yellow fruits of the cornelian cherry and loganic acid obtained from yellow fruits at a dose of 20 mg/kg of body weight for 14 days. On the 24th day of the experiment, the rats were decapitated under ether anesthesia, and blood was taken. The content of pyruvate and lactate (as the end products of anaerobic glycolysis) and L-lactate dehydrogenase activity were determined in plasma and erythrocytes, as well as biochemical markers of the antioxidant status of erythrocytes (activity of superoxide dismutase, catalase and glutathione peroxidase, level of reduced glutathione, TBA-reactive substances, concentration of oxidative modifications of proteins and advanced oxidation protein products). Results. The activity of catalase, superoxide dismutase, glutathione peroxidase and the concentration of reduced glutathione significantly increased against the decrease in the content of oxidative modifications of proteins, advanced oxidation protein products, TBA-reactive substances, pyruvate, L-lactate, and lactate dehydrogenase in rats with DM after administration of the fruit extracts of the cornelian cherry. Noteworthy, these biochemical indicators made it possible to assess the intensity of anaerobic glycolysis and the antioxidant status of blood erythrocytes in streptozotocin diabetes. Conclusions. Extracts of Cornus mas L. fruits might be potential natural drugs for the treatment of metabolic disorders in diabetes, as they have a corrective effect on the catabolic breakdown of glucose and the antioxidant defense system of erythrocytes, preventing the development of oxidative stress. It should be pointed out that the extract of red fruits of cornelian cherry showed the best effect among the studied extracts in normalizing these indicators.

Unveiling the crucial role of intercellular adhesion molecule-1 in secondary diabetic complications.

Diabetes mellitus is associated with secondary complications such as diabetic retinopathy (DR), nephropathy (DN), and cardiomyopathy (DCM), all of which significantly impact patient health. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory responses and endothelial dysfunction, both crucial in the pathogenesis of these complications. The goal of this review is to investigate at potential therapy methods that target ICAM-1 pathways and to better understand the multifaceted role of ICAM-1 in secondary diabetic problems. A meticulous analysis of scholarly literature published globally was conducted to examine ICAM-1involvement in inflammatory processes, endothelial dysfunction, and oxidative stress related to diabetes and its complications. Elevated ICAM-1 levels are strongly associated with augmented leukocyte adhesion, compromised microvascular function, and heightened oxidative stress in diabetes. These pathways contribute significantly to DR, DN, and DCM pathogenesis, highlighting ICAM-1 as a key player in their progression. Understanding ICAM-1 role in secondary diabetic complications offers insights into novel therapeutic strategies. Targeting ICAM-1 pathways may mitigate inflammation, improve endothelial function, and ultimately attenuate diabetic complications, thereby enhancing patient health outcomes. Continued research in this area is crucial for developing effective targeted therapies.

The Effect of Cerium Oxide (CeO2) on Ischemia-Reperfusion Injury in Skeletal Muscle in Mice with Streptozocin-Induced Diabetes.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO2) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes-CeO2 (group DCO, n = 8), diabetes-ischemia/reperfusion (group DIR, n = 8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO2 of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia-120 min reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p < 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p < 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p < 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO2, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice.

Effect of Modified Diets Pancreatic Oxidative Markers in Streptozotocin-Induced Diabetic Wistar rats Following the Administration of Alpha Lipoic Acid

Despite the availability of various anti-diabetic drugs, diabetes mellitus (DM) remains one of the world’s most prevalent chronic diseases leading to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. This study aimed to investigate the ameliorative effect of modified diets on pancreatic oxidative markers in streptozotocin-induced diabetic Wistar rats following the administration of Alpha lipoic acid, using standard appropriate techniques. Result established that High protein diet (HPD), and with combined administration with alpha lipoic acid in this research resulted in an increased pancreatic superoxide dismutase (SOD) and catalase (CAT) and glutathione (GSH) levels respectively while decreasing pancreatic malondialdehyde (MDA) levels, hence is affirmed as a beneficial strategy in the management of oxidative stress in diabetes. The present study concludes that high protein diets alone and in combination with ALA decreases pancreatic oxidative stress damage caused by streptozotocin toxicity, hence, has the potential to manage diabetes by reducing Reactice oxygen species (ROS) mediated oxidative stress.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

Diabetic cardiomyopathy (DCM) is a major complication of diabetes. Transient receptor potential melastatin 2 (TRPM2) activity increases in diabetic oxidative stress state, and it is involved in myocardial damage and repair. We explore the protective effect of TRPM2 knockdown on the progression of DCM. A type 2 diabetes animal model was established in C57BL/6N mice by long-term high-fat diet (HFD) feeding combined with a single injection of 100-mg/kg streptozotocin (STZ). Genetic knockdown of TRPM2 in heart was accomplished by the intravenous injection via the tail vein of adeno-associated virus type 9 carrying TRPM2 shRNA. Neonatal rat ventricular myocytes was exposed to 45 mM of high-glucose (HG) stimulation for 72 h in vitro to mimic the in vivo conditions. Western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry and fluorescence, electron, CCK-8, and flow cytometry were used to evaluate the phenotype of cardiac inflammation, fibrosis, apoptosis, and autophagy. Mice with HFD/STZ-induced diabetes exhibited systolic and diastolic dysfunction, as demonstrated by increased myocardial apoptosis and autophagy inhibition in the heart. Compared to control group, the protein expression of TRPM2, bax, cleaved caspase-3, and P62 was significantly elevated, and the protein expression of bcl-2 and LC3-II was significantly decreased in the myocardial tissues of the HFD/STZ-induced diabetes group. Knockdown of TRPM2 significantly reversed the HFD/STZ-induced myocardial apoptosis and autophagy inhibition. TRPM2 silencing attenuated HG-induced apoptosis and autophagy inhibition in primary cardiomyocytes via regulating the MEK/ERK mTORC1 signaling pathway. TRPM2 knockdown attenuates hyperglycemia-induced myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice or HG-stimulated cardiomyocytes via regulating the MEK/ERK and mTORC1 signaling pathway.

Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway.

Diabetes is associated with increased oxidative stress, leading to altered tight junction formation and increased apoptosis in colonic epithelial cells. These changes may lead to intestinal barrier dysfunction and corresponding gastrointestinal symptoms in patients with diabetes, including diarrhea. The aim of this study was to characterize the effect and mechanism of Resolvin D1 (RvD1) on diabetes-induced oxidative stress and barrier disruption in the colon. Mice with streptozotocin-induced diabetes were treated with RvD1 for 2 weeks, then evaluated for stool frequency, stool water content, gut permeability, and colonic transepithelial electrical resistance as well as production of reactive oxygen species (ROS), apoptosis, and expression of tight junction proteins Zonula Occludens 1 (ZO-1) and occludin. The same parameters were assessed in human colonoid cultures subjected to elevated glucose. We found that RvD1 treatment did not affect blood glucose, but normalized stool water content and prevented intestinal barrier dysfunction, epithelial oxidative stress, and apoptosis. RvD1 also restored ZO-1 and occludin expression in diabetic mice. RvD1 treatment increased phosphorylation of Akt and was accompanied by a 3.5-fold increase in heme oxygenase-1 (HO-1) expression in the epithelial cells. The protective effects of RvD1 were blocked by ZnPP, a competitive inhibitor of HO-1. Similar findings were observed in RvD1-treated human colonoid cultures subjected to elevated glucose. In conclusion, Oxidative stress in diabetes results in mucosal barrier dysfunction, contributing to the development of diabetic diarrhea. Resolvins prevent ROS-mediated mucosal injury and protect gut barrier function by intracellular PI3K/Akt activation and subsequent HO-1 upregulation in intestinal epithelial cells. These actions result in normalizing stool frequency and stool water content in diabetic mice, suggesting that resolvins may be useful in the treatment of diabetic diarrhea.

Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through pharmacological interventions.

Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates. The majority of cases of diabetes in 2021 (>90.0%) were type 2 diabetes, which is largely indicative of the prevalence of diabetes in general, particularly in older adults (K. L. Ong, et al., Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021, Lancet, 2023, 402(10397), 203-234). Nowadays, slowing the progression of diabetic complications is the only effective way to manage diabetes with the available therapeutic options. However, novel biomarkers and treatments are urgently needed to control cytokine secretion, advanced glycation end products (AGEs) production, vascular inflammatory effects, and cellular death. Emerging research has highlighted the intricate interplay between reactive oxygen species (ROS) and protein aggregation in the pathogenesis of diabetes. In this scenario, the main aim of this paper is to provide a comprehensive review of the current understanding of the molecular mechanisms underlying ROS-induced cellular damage and protein aggregation, specifically focusing on their contribution to diabetes development. The role of ROS as key mediators of oxidative stress in diabetes is discussed, emphasizing their impact on cellular components and signaling. Additionally, the involvement of protein aggregation in impairing cellular function and insulin signaling is explored. The synergistic effects of ROS and protein aggregation in promoting β-cell dysfunction and insulin resistance are examined, shedding light on potential targets for therapeutic intervention.

Structural changes in testes of Streptozotocin induced diabetic rats and possible protective effect of royal jelly: light and electron microscopic study

ABSTRACT Diabetes mellitus (DM) is one of the most common metabolic diseases causing damage in many organs in the body including the testes. Royal Jelly (RJ) is one of the honey bee products that has antioxidant, anti-inflammatory and antidiabetic properties. This study was performed to evaluate the changes in the microscopic structure of the testes in Streptozotocin (STZ)-induced diabetic rats, and the possible protective role of RJ. 60 adult male albino rats were divided into three groups. Group I Control group, Group II STZ group, and Group III STZ+RJ group. Group II received a single dose of STZ (50 mg/kg) by intraperitoneal injection. Group III received a single dose of STZ as in the second group then received RJ orally by intragastric tube in dose of (100 mg/kg/day) for 4 weeks after confirmation of diabetes. Light and electron microscopic studies were performed. Group II revealed marked structural changes affecting seminiferous tubules with sever reduction in germinal epithelium and loss of mature spermatozoa in their lumina. The interstitial tissue revealed degenerated Leydig cells and congested blood vessels. Mallory trichrome stained section of group II revealed marked increase in the amount of collagen fibers. Group III revealed highly preserved testicular architecture almost near to that appeared in the control group except few tubules that were damaged. In conclusion, RJ protected the testicular structure from the damaging effect of diabetic oxidative stress through its antioxidant effect thus preserving male fertility.

Anti-oxidative and anti-inflammatory activity of Achatina fulica mucus in streptozocin-nicotinamide-induced diabetic kidney disease: an animal model study

Introduction: Diabetic kidney disease (DKD) progression resulted in increased intrarenal oxidative stress and increased inflammatory resulting in further renal fibrosis. Achatina fulica mucus was regarded to exerts anti-oxidative and anti-inflammatory effect. Objectives: This study aims to observe the effect of administration of A. fulica mucus on oxidative stress and inflammation biomarkers in DKD-induced rats. Methods and Materials: In this study, we used 32 males white Wistar rats divided into four groups; a control, and other three different groups induced with 45 mg/kg streptozocin (STZ) and 110 mg/kg nicotinamide (NA) intra-peritoneally. Achatina fulica mucus was administered orally in the last groups; 3.5 mL/d (S1), and 7 mL/d (S2). Post-test measurement of inflammatory and oxidative biomarker was used to determine the outcome. Results: The study resulted in reduction of malondialdehyde (MDA), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), high sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), and interleukin-1β (IL-1β) in A. fulica mucus administration in our STZ-NA induced rats, with higher dose of the mucus further reduce the inflammatory and oxidative stress biomarkers. Conclusion: Current study showed the potential of A. fulica mucus usage in future management of inflammation and oxidative stress in diabetes and DKD.

Examining the Effects of Hyperbaric Oxygen Therapy on the Cardiovascular System and Oxidative Stress in Insulin-Treated and Non-Treated Diabetic Rats.

This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

Diabetes and Ethnomedicine a Comprehensive Review of Scientific Literature on Traditional Medical Practices

Ethnomedicine, the traditional medical practices and beliefs of a particular cultural or ethnic group, may offer cost-effective and culturally acceptable treatment options for diabetes. Ethnomedicine encompasses various traditional healing practices, such as herbalism, acupuncture, and massage therapy. This article reviews the current evidence-based state of ethnomedicine for diabetes, focusing on the efficacy, safety, and mechanisms of action of selected ethnomedical interventions. The results indicate that some ethnomedical practices, such as herbal remedies and dietary interventions, may have beneficial effects on glycaemic control, insulin sensitivity, and oxidative stress in diabetes. However, the evidence is inconsistent and limited by methodological flaws, such as small sample size, lack of control group, and inadequate reporting. Moreover, some ethnomedical interventions may pose significant risks, such as drug interactions and adverse effects. Therefore, it is essential that patients consult with their healthcare provider before using any ethnomedical interventions for diabetes and that these interventions be rigorously evaluated using scientific methods.

Evaluation of Non Enzymatic Status in Antioxidant Capital in Senegalese Type 2 Diabetics

Oxidative stress appears very early in the history of type 2 diabetes complications. It is associated to glucose oxidation but also to lipid peroxidation. This stress can be accentuated by a decrease in the antioxidant capacities in diabetics, especially if there are other comorbidities. The objective of this study was to evaluate the antioxidant capacity of Senegalese type 2 diabetics and to identify the associated risk factors.&#x0D; We conducted a prospective study in 40 persons with type 2 diabetes. Factors related to age, sex, BMI, and BP were determined. For biological parameters, we measured blood glucose at empty stomach, glycated haemoglobin, total cholesterol, HDL, triglycerides and LDL, urea and creatinine, uric acid, albumin, total bilirubin, copper, and zinc.&#x0D; The mean age of the population was 58±11.24 years with a predominance of subjects aged over 60 (52.5%). The sex ratio was 1.11 with 52.5% male. Antioxidant capital was reduced in 60% of patients, with a predominance of women (35%). This reduction was marked by hypoalbuminemia (32.5%), hypozincemia (22.5) and an increase in the Cu/Zn ratio (30%). A strong correlation was found between the Cu/Zn ratio and total cholesterol (r=0.911; p&lt;0.0001) as well as LDL (r=1; p=0.0001). Dyslipidaemia was found to be the most associated comorbidity with decreased oxidative capacity with an RR of 1.4 (CI=0.79-2.35) for total hypercholesterolemia and an RR of 1.6 (CI=0.75-3.71) for hypertriglyceridemia.&#x0D; The antioxidant capital is reduced in type 2 diabetics, especially in dyslipidaemia conditions. Hygienic dietary measures and supplementation with trace elements such as zinc should prevent the complications of oxidative stress in diabetics.

Conglutin Gamma, A Lupin Seed Protein Reduces Oxidative Stress in Diabetics

Conglutin Gamma, A Lupin Seed Protein Reduces Oxidative Stress in Diabetics

Mechanistic insights on anserine hydrolyzing activities of human carnosinases

Anserine and carnosine represent histidine-containing dipeptides that exert a pluripotent protective effect on human physiology. Anserine is known to protect against oxidative stress in diabetes and cardiovascular diseases. Human carnosinases (CN1 and CN2) are dipeptidases involved in the homeostasis of carnosine. In poikilothermic vertebrates, the anserinase enzyme is responsible for hydrolyzing anserine. However, there is no specific anserine hydrolyzing enzyme present in humans. In this study, we have systematically investigated the anserine hydrolyzing activity of human CN1 and CN2. A targeted multiple reaction monitoring (MRM) based approach was employed for studying the enzyme kinetics of CN1 and CN2 using carnosine and anserine as substrates. Surprisingly, both CN1 and CN2 can hydrolyze anserine effectively. The observed catalytic turnover rate (Vmax/[E]t) was 21.6 s−1 and 2.8 s−1 for CN1 and CN2, respectively. CN1 is almost eight-fold more efficient in hydrolyzing anserine compared to CN2, which is comparable to the efficiency of the carnosine hydrolyzing activity of CN2. The Michaelis constant (Km) value for CN1 (1.96 mM) is almost three-fold lower compared to CN2 (6.33 mM), representing higher substrate affinity for anserine-CN1 interactions. Molecular docking studies showed that anserine binds at the catalytic site of the carnosinases with an affinity similar to carnosine. Overall, the present study elucidated the inherent promiscuity of human carnosinases in hydrolyzing anserine using a sensitive LC-MS/MS approach.

The ABC (HbA1c, blood pressure and LDL-cholesterol) of diabetes and oxidative stress: knowing the links

Introduction and Aim: Large body of evidence suggests that oxidative stress has a crucial role to play in diabetes and its related complications. In the present research we have tried to determine potential risk factors for oxidative stress in type 2 diabetes by conducting a cross-sectional study. Materials and Methods: We studied 238 patients with or without complications of diabetes, aged 40-75 years. Blood samples were analysed for fasting plasma glucose, glycated haemoglobin, malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. Each patient’s waist circumference, BMI, blood pressure was measured. Results: Participants mean age was 57.5 ± 8.9 years. Logistic regression analysis identified glycated haemoglobin (95% CI: 1.02-1.92; p=0.04), hypertension (95% CI: 0.99-4.08; p=0.05) and LDL-cholesterol (95% CI: 1.12-5.87; p=0.03) as independent risk factors for oxidative stress. Other contributors were age and presence of complications like nephropathy, retinopathy, peripheral neuropathy and macrovascular disease in diabetes. Conclusion: Our data demonstrate that ‘ABCs of diabetes’ namely HbA1c, blood pressure and LDL-cholesterol are independent risk factors for oxidative stress. Oxidative stress aggravates with age and presence of complications. It appears important to achieve a good ABC goal to bring down oxidative stress in diabetes.

Effects of zinc supplementation on glycemic control and oxidative stress in experimental diabetes: A systematic review.

Diabetes mellitus (DM), an important public health problem worldwide, can cause imbalances in the homeostasis of trace elements such as zinc (Zn). It is possible that an adequate nutritional status related to nutrients is essential for the normal functioning of antioxidant defense systems, and any change in the concentration of these substances could increase the chances of DM complications. To present a review on the effect of zinc supplementation on glycemic control and oxidative stress in experimental diabetes. This is a systematic review of articles that investigated the effects of zinc supplementation on glycemic control and oxidative stress in diabetic rats. The PICOS strategy was used for the development of the research question, and the Syrcle tool for the quality assessment of the studies included in the review. Articles available in the PubMed, Scopus, and Web of Science databases were included without restriction on year of publication. The Syrcle tool was used to assess the risk of bias of the included studies. Fifteen studies were included in the review, seven of which evaluated glycemic control and oxidative stress after zinc supplementation, five only oxidative stress and three only glycemic control after zinc treatment. In all the studies included, diabetes was induced by the administration of streptozotocin (STZ) at doses ranging from 40 to 100mg/kg. Zinc supplementation was made in the diet or drinking water or by gavage or intraperitoneal injection. The most used doses were 100mg/kg of body weight by gavage and 0.32 and 0.64g/kg in diet. The supplementation period ranged from 14 days to 8 weeks. Six studies revealed that zinc supplementation decreased fasting blood glucose as well as insulin resistance; nine studies included in this review reported decreased MDA concentration; in five studies, there was an increase in the activity of antioxidant enzymes (GPx, SOD, GSH and catalase); and one of the studies reported a reduction in glycated hemoglobin. Zinc supplementation improved hyperglycemia and revealed a protective potential against oxidative stress associated with experimental diabetes.

Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice.

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2′,7′-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.