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Targeting Oxidative Stress and Organites Associated in Disease

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 13965

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Special Issue Editor

Dr. Anne Vejux

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Guest Editor

Team ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ EA7270/Inserm, University Bourgogne Franche-Comté, 21000 Dijon, France
Interests: apoptosis; autophagy; oxysterols; lipids; neurodegenerative diseases; inflammation; oxidative stress
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Special Issue Information

Dear Colleagues,

Oxidative stress is a metabolic dysfunction mediated by the imbalance between biochemical processes leading to a high production of reactive oxygen and/or nitrogen species and the body's antioxidant defense system. It plays a preponderant role in the development of many diseases that have a strong impact on the health system, including cardiovascular diseases, cancers, neurodegenerative diseases, aging, eye diseases and respiratory diseases. Oxidative damage can be in the form of lipid peroxidation, free radical attack of proteins, DNA damage, etc., and is strongly linked to other important mechanisms in pathophysiology such as autophagy, apoptosis, and inflammation.

During normal metabolism, the tetravalent reduction of oxygen to water occurs in several successive steps that give rise to potentially reduced intermediates—the reactive oxygen species. The degradation of these radicals is controlled by defense systems—the antioxidants. The production of superoxide radicals is regulated by metalloenzymes (the superoxide dismutases), which catalyze their dismutation into hydrogen peroxide, H₂O₂, which is toxic and capable of giving rise to the most deleterious of the radical species of oxidative stress, the hydroxyl radical OH, via reactionsof the "Fenton reaction" type. The amount of hydrogen peroxide is regulated by the heme enzyme catalase, which accelerates its dismutation, and by glutathione peroxidase, which catalyzes its reduction by glutathione. There are also other ROS, called secondary ROS, such as peroxyl radicals RO₂•, hydroperoxides RO₂H and alkoxyl radicals RO•. The organelles which are mainly involved are the mitochondria and the peroxisome.

In the context of the different pathologies mentioned, it is important to know the pathways that lead to oxidative stress, the interactions with other pathophysiological mechanisms, how the organelles are involved, how they interact, and above all how this oxidative stress can be targeted via synthetic molecules or via molecules of natural origin. It may also be interesting to study relevant antioxidant biomarkers and the potential of predictive diagnostics.

Dr. Anne Vejux
Guest Editor

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Keywords

oxidative stress
mitochondria
peroxisome
antioxidant
therapy
biomarkers

Published Papers (5 papers)

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Research

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30 pages, 9734 KiB

Open AccessArticle

Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane

by Abbirami Balachandran, Sy Bing Choi, Morak-Młodawska Beata, Jeleń Małgorzata, Gabriele R. A. Froemming, Charlie A. Lavilla, Jr., Merell P. Billacura, Stepfanie N. Siyumbwa and Patrick N. Okechukwu

Molecules 2023, 28(3), 1043; https://doi.org/10.3390/molecules28031043 - 20 Jan 2023

Cited by 21 | Viewed by 4333

Abstract

1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress and Organites Associated in Disease)

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14 pages, 2303 KiB

Open AccessArticle

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

by Abdelrahim Alqudah, Esam Y. Qnais, Mohammed A. Wedyan, Sara Altaber, Yousra Bseiso, Muna Oqal, Rawan AbuDalo, Khaled Alrosan, Amjad Z. Alrosan, Suhad Bani Melhim, Mohammad Alqudah, Rabaa Y. Athamneh and Omar Gammouh

Molecules 2023, 28(2), 502; https://doi.org/10.3390/molecules28020502 - 04 Jan 2023

Cited by 9 | Viewed by 2437

Abstract

Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress and Organites Associated in Disease)

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16 pages, 2067 KiB

Open AccessArticle

Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells

by Mohamed Ksila, Anne Vejux, Emmanuelle Prost-Camus, Philippe Durand, Imen Ghzaiel, Thomas Nury, Dorian Duprey, Smail Meziane, Olfa Masmoudi-Kouki, Norbert Latruffe, Taoufik Ghrairi, Michel Prost, Gérard Lizard and Dominique Vervandier-Fasseur

Molecules 2022, 27(15), 4713; https://doi.org/10.3390/molecules27154713 - 23 Jul 2022

Cited by 2 | Viewed by 1791

Abstract

Trans-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans-resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans-resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC₆(3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2′-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans-resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans-resveratrol. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress and Organites Associated in Disease)

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Review

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13 pages, 647 KiB

Open AccessReview

Pharmacological Modulations of Nrf2 and Therapeutic Implications in Aneurysmal Subarachnoid Hemorrhage

by Qia Zhang, Jianmin Zhang and Jun Mo

Molecules 2023, 28(4), 1747; https://doi.org/10.3390/molecules28041747 - 12 Feb 2023

Viewed by 1748

Abstract

An aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of stroke with high morbidity and mortality. The main causes of a poor prognosis include early brain injury (EBI) and delayed vasospasm, both of which play a significant role in the pathophysiological process. As an important mechanism of EBI and delayed vasospasm, oxidative stress plays an important role in the pathogenesis of aSAH by producing reactive oxygen species (ROS) through the mitochondria, hemoglobin, or enzymatic pathways in the early stages of aSAH. As a result, antioxidant therapy, which primarily targets the Nrf2-related pathway, can be employed as a potential strategy for treating aSAH. In the early stages of aSAH development, increasing the expression of antioxidant enzymes and detoxifying enzymes can relieve oxidative stress, reduce brain damage, and improve prognosis. Herein, the regulatory mechanisms of Nrf2 and related pharmacological compounds are reviewed, and Nrf2-targeted drugs are proposed as potential treatments for aSAH. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress and Organites Associated in Disease)

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15 pages, 1427 KiB

Open AccessReview

The Role of Oxidative Stress-Mediated Inflammation in the Development of T2DM-Induced Diabetic Nephropathy: Possible Preventive Action of Tannins and Other Oligomeric Polyphenols

by Gohar Sahakyan, Anne Vejux and Naira Sahakyan

Molecules 2022, 27(24), 9035; https://doi.org/10.3390/molecules27249035 - 18 Dec 2022

Cited by 16 | Viewed by 2725

Abstract

Diabetic nephropathy is manifested in more than 10% of people with diabetes. It is a common cause of kidney failure and end-stage kidney disease. Understanding of mechanisms underlying the initiation and development of diabetes-induced kidney injuries will allow for the development of more effective methods of prevention and treatment of the disease. Diabetic nephropathy is a wide-ranging complication of diabetes, and it is necessary to discuss the “weight” of pro-inflammatory pathways and molecules in the progress of renal injuries during the development of the disease. A large spectrum of pro-inflammatory molecules and pathways participate in different stages of the pathophysiological progression of diabetic nephropathy, including pro-inflammatory cytokines, chemokines, their receptors, adhesion molecules, and transcription factors. On the other hand, it is known that one of the consequences of hyperglycemia-induced ROS generation is the up-regulation of pro-inflammatory cascades, which, in turn, activate the transcription of genes encoding cytokines-chemokines, growth factors, and extracellular matrix proteins. It is a proven fact that a variety of plant secondary metabolites, such as tannins, flavonoids, and other polyphenols, demonstrate significant anti-diabetic, redox-modulating properties and effectively modulate the inflammatory response. Thus, this review is discussing the possible role of plant phenols in the prevention and treatment of diabetic nephropathy. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress and Organites Associated in Disease)

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