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

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editors

Dr. Laura Sabatino
E-Mail Website
Guest Editor
Istituto di Fisiologia Clinica del CNR, Pisa, Italy
Interests: enzymes activation/deactivation; gene expression; protein levels evaluation
Special Issues, Collections and Topics in MDPI journals
Dr. Melania Gaggini
E-Mail
Guest Editor
Fondazione Regione Toscana G. Monasterio, 56124 Pisa, Italy
Dr. Kyriazoula Chatzianagnostou
E-Mail Website
Guest Editor
Fondazione Regione Toscana G. Monasterio, 56124 Pisa, Italy

Special Issue Information

Dear Colleagues,

Type 2 diabetes (T2D) is the most common chronic metabolic disease. There is strong evidence of interrelationships between oxidative stress and inflammation and molecular and cellular events related to T2D onset, progression, and complications.  However, the terms “oxidative stress” and “inflammation” imply a number of different molecular and cellular pathways, regarding, for example, endothelial dysfunction,  mitochondrial DNA structure,  enzyme activity, and gene expression. Thus, it is clear that a unique, universally applicable biomarker does not exist. Moreover, the significance of a given biomarker might not be the same in the different stages of the disease. Thus, the identification of additional pathways/biomarkers involved in T2D pathophysiology might provide new insights into the onset and development of the disease and its complications, favoring the characterization of new targeted therapeutic approaches for more focused personalized medicine.

In this scenario, additional integrative antioxidant compounds could act as coadjuvants to traditional pharmacological tools, providing more potential therapeutic benefits for the treatment of T2D. However, possible health detrimental effects of antioxidant molecules can also develop. 

We invite  contributions in the form of both original articles and review manuscripts focusing on the study of  oxidative/inflammatory-related mechanisms involved in T2D pathophysiology or discussing biomarkers identification, validation, and implementation and their possible role as targets for therapeutic strategies against T2D. Potential topics include, but are not limited, to:

  • known and newly identified oxidative stress/inflammatory-related processes contributing to a better understanding of T2D pathophysiology;
  • oxidative/inflammatory biomarkers in T2D: pathophysiological significance and potential utility in the clinical practice towards personalized medicine approaches
  • antioxidant therapeutic strategies against T2D

Dr. Cristina Vassalle
Dr. Laura Sabatino
Dr. Melania Gaggini
Dr. Kyriazoula Chatzianagnostou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

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Communication
Does Empagliflozin Modulate Leukocyte–Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?
Antioxidants 2021, 10(8), 1228; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081228 - 30 Jul 2021
Viewed by 511
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
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Article
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
Antioxidants 2021, 10(7), 1086; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071086 - 06 Jul 2021
Viewed by 768
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 AMPKT172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPKT172 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
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Article
Substance-P Inhibits Cardiac Microvascular Endothelial Dysfunction Caused by High Glucose-Induced Oxidative Stress
Antioxidants 2021, 10(7), 1084; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071084 - 05 Jul 2021
Cited by 1 | Viewed by 620
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
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Article
Rice Husk Silica Liquid Protects Pancreatic β Cells from Streptozotocin-Induced Oxidative Damage
Antioxidants 2021, 10(7), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071080 - 05 Jul 2021
Viewed by 1061
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
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Article
Effects of Rutin on Wound Healing in Hyperglycemic Rats
Antioxidants 2020, 9(11), 1122; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111122 - 13 Nov 2020
Cited by 7 | Viewed by 1113
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
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Review

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Review
Oxidative Stress Biomarkers in the Relationship between Type 2 Diabetes and Air Pollution
Antioxidants 2021, 10(8), 1234; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081234 - 30 Jul 2021
Viewed by 602
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
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