Editorial

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Open AccessEditorial

Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options

by Cristina Vassalle and Melania Gaggini

Antioxidants 2022, 11(5), 953; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11050953 - 12 May 2022

Cited by 9 | Viewed by 1380

Type 2 diabetes (T2D) is a public health burden associated with high healthcare and societal costs and elevated morbidity and mortality [...] Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

Research

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10 pages, 880 KiB

Open AccessCommunication

Does Empagliflozin Modulate Leukocyte–Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?

by Francisco Canet, Francesca Iannantuoni, Aránzazu Martínez de Marañon, Pedro Díaz-Pozo, Sandra López-Domènech, Teresa Vezza, Blanca Navarro, Eva Solá, Rosa Falcón, Celia Bañuls, Carlos Morillas, Milagros Rocha and Víctor M. Víctor

Antioxidants 2021, 10(8), 1228; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081228 - 30 Jul 2021

Cited by 13 | Viewed by 2709

Abstract

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric [...] Read more.

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte–endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression. According to standard clinical protocols, sixteen T2D patients receiving 10 mg/day of empagliflozin were followed-up for 24 weeks. Anthropometric and analytical measurements were performed at baseline, 12 weeks, and 24 weeks. Interactions between polymorphonuclear leukocytes and human umbilical vein endothelial cells (HUVECs), serum levels of adhesion molecules (P-Selectin, VCAM-1 and ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), mitochondrial ROS levels, antioxidant enzymes (SOD1 and GPX1), and NFkB-p65 were measured. We observed a decrease in body weight, BMI, and HbA1C levels from 12 weeks of treatment, which became more pronounced at 24 weeks and was accompanied by a significant reduction in waist circumference and glucose. Leukocyte–endothelium interactions were reduced due to an enhancement in the leukocyte rolling velocity from 12 weeks onwards, together with a significant decrease in leukocyte rolling flux and adhesion at 24 weeks. Accordingly, a significant decrease in ICAM-1 levels, mitochondrial ROS levels, and IL-6 and NFkB-p65 expression was observed, as well as an increase in SOD1. This pilot study provides evidence of the anti-inflammatory and antioxidant properties of empagliflozin treatment in humans, properties which may underlie its beneficial cardiovascular effects. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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14 pages, 4803 KiB

Open AccessArticle

3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus

by Tsung-Tien Wu, Ying-Ying Chen, Chiu-Yi Ho, Tung-Chen Yeh, Gwo-Ching Sun, Ching-Jiunn Tseng and Pei-Wen Cheng

Antioxidants 2021, 10(7), 1086; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071086 - 06 Jul 2021

Cited by 9 | Viewed by 2441

Abstract

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs [...] Read more.

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPK^T172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPK^T172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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12 pages, 2021 KiB

Open AccessArticle

Substance-P Inhibits Cardiac Microvascular Endothelial Dysfunction Caused by High Glucose-Induced Oxidative Stress

by Do Young Kim, Jiyuan Piao and Hyun Sook Hong

Antioxidants 2021, 10(7), 1084; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071084 - 05 Jul 2021

Cited by 14 | Viewed by 2246

Abstract

Diabetes is characterized by high glucose (HG) levels in the blood circulation, leading to exposure of the vascular endothelium to HG conditions. Hyperglycemia causes oxidative stress via excessive reactive oxygen species (ROS) production in the endothelium, which leads to cellular dysfunction and the [...] Read more.

Diabetes is characterized by high glucose (HG) levels in the blood circulation, leading to exposure of the vascular endothelium to HG conditions. Hyperglycemia causes oxidative stress via excessive reactive oxygen species (ROS) production in the endothelium, which leads to cellular dysfunction and the development of diabetic vascular diseases. Substance-P (SP) is an endogenous peptide involved in cell proliferation and migration by activating survival-related signaling pathways. In this study, we evaluated the role of SP in cardiac microvascular endothelial cells (CMECs) in HG-induced oxidative stress. CMECs were treated with diverse concentrations of glucose, and then the optimal dose was determined. Treatment of CMECs with HG reduced their viability and induced excessive ROS secretion, inactivation of PI3/Akt signaling, and loss of vasculature-forming ability in vitro. Notably, HG treatment altered the cytokine profile of CMECs. However, SP treatment inhibited the HG-mediated aggravation of CMECs by restoring viability, free radical balance, and paracrine potential. SP-treated CMECs retained the capacity to form compact and long stretching-tube structures. Collectively, our data provide evidence that SP treatment can block endothelial dysfunction in hyperglycemia and suggest the possibility of using SP for treating diabetic complications as an antioxidant. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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13 pages, 2689 KiB

Open AccessArticle

Rice Husk Silica Liquid Protects Pancreatic β Cells from Streptozotocin-Induced Oxidative Damage

by Hsin-Yuan Chen, Yi-Fen Chiang, Kai-Lee Wang, Tsui-Chin Huang, Mohamed Ali, Tzong-Ming Shieh, Hsin-Yi Chang, Yong-Han Hong and Shih-Min Hsia

Antioxidants 2021, 10(7), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071080 - 05 Jul 2021

Cited by 6 | Viewed by 2993

Abstract

Type 2 diabetes mellitus is a complex multifactorial disease characterized by insulin resistance and dysfunction of pancreatic β-cells. Rice husk silica liquid (RHSL) is derived from rice husks and has not been explored in diabetes mellitus until now. Previous studies showed that rice [...] Read more.

Type 2 diabetes mellitus is a complex multifactorial disease characterized by insulin resistance and dysfunction of pancreatic β-cells. Rice husk silica liquid (RHSL) is derived from rice husks and has not been explored in diabetes mellitus until now. Previous studies showed that rice husk is enriched with silica, and its silica nanoparticles are higher more biocompatible. To investigate the potential protective role of RHSL on pancreatic β cells, we utilized RIN-m5F pancreatic β cells and explored RHSL effect after streptozotocin (STZ)-stimulation. The recovery effects of RHSL were evaluated using flow cytometry, Western blotting, and immunofluorescence analysis. Results of our study showed that RHSL reversed the cell viability, insulin secretion, reactive oxygen species (ROS) production, and the change of mitochondria membrane potential (ΔΨm) in STZ-treated RIN-m5F cells. Moreover, the expression of phospho-receptor-interacting protein 3 (p-RIP3) and cleaved-poly (ADP-ribose) polymerase (PARP), phospho-mammalian target of rapamycin (p-mTOR), and sequestosome-1 (p62/SQSTM1) were significantly decreased, while the transition of light chain (LC)3-I to LC3-II was markedly increased after RHSL treatment in STZ-induced RIN-m5F cells. Interestingly, using autophagy inhibitors such as 3-methyladenine (3-MA) and chloroquine (CQ) both showed an increase in cleaved-PARP protein level, indicating apoptosis induction. Taken together, this study demonstrated that RHSL induced autophagy and alleviated STZ-induced ROS-mediated apoptosis in RIN-m5F cells. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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13 pages, 7573 KiB

Open AccessArticle

Effects of Rutin on Wound Healing in Hyperglycemic Rats

by Li-You Chen, Chien-Ning Huang, Chih-Kai Liao, Hung-Ming Chang, Yu-Hsiang Kuan, To-Jung Tseng, Kai-Jung Yen, Kai-Lin Yang and Hsing-Chun Lin

Antioxidants 2020, 9(11), 1122; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111122 - 13 Nov 2020

Cited by 45 | Viewed by 4755

Abstract

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on [...] Read more.

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on wound healing in streptozotocin-induced hyperglycemic rats. Eighteen male Wistar rats were randomly divided into three groups: normal (NDM), hyperglycemic (DM), and hyperglycemic with rutin (DMR). After induction of hyperglycemia for 2 days, a 15 × 15 mm wound was induced on the back of each rat. Intraperitoneal injection of rutin significantly ameliorated diabetes-induced body weight loss and improved metabolic dysfunctions of hyperglycemic rats. Based on appearance and histopathological staining, rutin promotes wound healing and inhibits production of inflammatory cells. The immunoblotting data indicated that rutin promotes production of antioxidant enzymes induced by nuclear factor erythroid 2-related factor 2 (NRF2), inhibits the expression of matrix metalloproteinases (MMPs) regulated by NF-κB, and decreases the expression of vascular endothelial growth factor (VEGF). It also promotes the expression of neurogenic-related protein (UCH-L1). The aforementioned results indicated that rutin reduces oxidative stress and inflammatory response in hyperglycemic rats, promoting wound healing and subsequently reducing the risk of wound ulcers. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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Review

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18 pages, 1835 KiB

Open AccessReview

Possible Gender Influence in the Mechanisms Underlying the Oxidative Stress, Inflammatory Response, and the Metabolic Alterations in Patients with Obesity and/or Type 2 Diabetes

by Martha Lucinda Contreras-Zentella and Rolando Hernández-Muñoz

Antioxidants 2021, 10(11), 1729; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111729 - 29 Oct 2021

Cited by 4 | Viewed by 3152

Abstract

The number of patients afflicted by type 2 diabetes and its morbidities has increased alarmingly, becoming the cause of many deaths. Normally, during nutrient intake, insulin secretion is increased and glucagon secretion is repressed, but when plasma glucose concentration increases, a state of [...] Read more.

The number of patients afflicted by type 2 diabetes and its morbidities has increased alarmingly, becoming the cause of many deaths. Normally, during nutrient intake, insulin secretion is increased and glucagon secretion is repressed, but when plasma glucose concentration increases, a state of prediabetes occurs. High concentration of plasma glucose breaks the redox balance, inducing an oxidative stress that promotes chronic inflammation, insulin resistance, and impaired insulin secretion. In the same context, obesity is one of the most crucial factors inducing insulin resistance, inflammation, and contributing to the onset of type 2 diabetes. Measurements of metabolites like glucose, fructose, amino acids, and lipids exhibit significant predictive associations with type 2 diabetes or a prediabetes state and lead to changes in plasma metabolites that could be selectively affected by gender and age. In terms of gender, women and men have biological dissimilarities that might have an important role for the development, diagnosis, therapy, and prevention of type 2 diabetes, obesity, and relevant hazards in both genders, for type 2 diabetes. Therefore, the present review attempts to analyze the influence of gender on the relationships among inflammatory events, oxidative stress, and metabolic alterations in patients undergoing obesity and/or type 2 diabetes. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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15 pages, 834 KiB

Open AccessReview

Oxidative Stress Biomarkers in the Relationship between Type 2 Diabetes and Air Pollution

by Francesca Gorini, Laura Sabatino, Melania Gaggini, Kyriazoula Chatzianagnostou and Cristina Vassalle

Antioxidants 2021, 10(8), 1234; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081234 - 30 Jul 2021

Cited by 13 | Viewed by 2870

Abstract

The incidence and prevalence of type 2 diabetes have increased in the last decades and are expected to further grow in the coming years. Chronic hyperglycemia triggers free radical generation and causes increased oxidative stress, affecting a number of molecular mechanisms and cellular [...] Read more.

The incidence and prevalence of type 2 diabetes have increased in the last decades and are expected to further grow in the coming years. Chronic hyperglycemia triggers free radical generation and causes increased oxidative stress, affecting a number of molecular mechanisms and cellular pathways, including the generation of advanced glycation end products, proinflammatory and procoagulant effects, induction of apoptosis, vascular smooth-muscle cell proliferation, endothelial and mitochondrial dysfunction, reduction of nitric oxide release, and activation of protein kinase C. Among type 2 diabetes determinants, many data have documented the adverse effects of environmental factors (e.g., air pollutants) through multiple exposure-induced mechanisms (e.g., systemic inflammation and oxidative stress, hypercoagulability, and endothelial and immune responses). Therefore, here we discuss the role of air pollution in oxidative stress-related damage to glycemic metabolism homeostasis, with a particular focus on its impact on health. In this context, the improvement of new advanced tools (e.g., omic techniques and the study of epigenetic changes) may provide a substantial contribution, helping in the evaluation of the individual in his biological totality, and offer a comprehensive assessment of the molecular, clinical, environmental, and epidemiological aspects. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Oxidative Stress and Inflammation: Pathophysiological Mechanisms and Possible Therapeutic Options)

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