International Journal of Molecular Sciences

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20 pages, 5768 KiB

Open AccessArticle

Diosmin Mitigates Cyclophosphamide Induced Premature Ovarian Insufficiency in Rat Model

by Noha M. Abogresha, Sally S. Mohammed, Marwa M. Hosny, Hoda Y. Abdallah, Ahmed M. Gadallah and Sahar M. Greish

Int. J. Mol. Sci. 2021, 22(6), 3044; https://doi.org/10.3390/ijms22063044 - 17 Mar 2021

Cited by 18 | Viewed by 5753

Abstract

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone [...] Read more.

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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14 pages, 2400 KiB

Open AccessArticle

Use of H₂O₂ to Cause Oxidative Stress, the Catalase Issue

by Céline Ransy, Clément Vaz, Anne Lombès and Frédéric Bouillaud

Int. J. Mol. Sci. 2020, 21(23), 9149; https://doi.org/10.3390/ijms21239149 - 30 Nov 2020

Cited by 183 | Viewed by 9536

Abstract

Addition of hydrogen peroxide (H₂O₂) is a method commonly used to trigger cellular oxidative stress. However, the doses used (often hundreds of micromolar) are disproportionally high with regard to physiological oxygen concentration (low micromolar). In this study using polarographic [...] Read more.

Addition of hydrogen peroxide (H₂O₂) is a method commonly used to trigger cellular oxidative stress. However, the doses used (often hundreds of micromolar) are disproportionally high with regard to physiological oxygen concentration (low micromolar). In this study using polarographic measurement of oxygen concentration in cellular suspensions we show that H₂O₂ addition results in O₂ release as expected from catalase reaction. This reaction is fast enough to, within seconds, decrease drastically H₂O₂ concentration and to annihilate it within a few minutes. Firstly, this is likely to explain why recording of oxidative damage requires the high concentrations found in the literature. Secondly, it illustrates the potency of intracellular antioxidant (H₂O₂) defense. Thirdly, it complicates the interpretation of experiments as subsequent observations might result from high/transient H₂O₂ exposure and/or from the diverse possible consequences of the O₂ release. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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15 pages, 3334 KiB

Open AccessArticle

New In Vitro Model of Oxidative Stress: Human Prostate Cells Injured with 2,2-diphenyl-1-picrylhydrazyl (DPPH) for the Screening of Antioxidants

by Christian Galasso, Concetta Piscitelli, Christophe Brunet and Clementina Sansone

Int. J. Mol. Sci. 2020, 21(22), 8707; https://doi.org/10.3390/ijms21228707 - 18 Nov 2020

Cited by 7 | Viewed by 2683

Abstract

The antioxidant activity of natural compounds consists in their ability to modulate gene and protein expression, thus inducing an integrated cell protective response and repair processes against oxidative stress. New screening tools and methodologies are crucial for the actual requirement of new products [...] Read more.

The antioxidant activity of natural compounds consists in their ability to modulate gene and protein expression, thus inducing an integrated cell protective response and repair processes against oxidative stress. New screening tools and methodologies are crucial for the actual requirement of new products with antioxidant activity to boost endogenous oxidative stress responsive pathways, Reactive Oxygen Species (ROS) metabolism and immune system activity, preserving human health and wellness. In this study, we performed and tested an integrated oxidative stress analysis, using DPPH assay and PNT2 cells injured with DPPH. We firstly investigated the mechanism of action of the oxidising agent (DPPH) on PNT2 cells, studying the variation in cell viability, oxidative stress genes, inflammatory mediator and ROS levels. The results reveal that DPPH activated ROS production and release of Prostaglandin E₂ in PNT2 at low and intermediate doses, while cells switched from survival to cell death signals at high doses of the oxidising agent. This new in vitro oxidative stress model was validated by using Trolox, β-carotene and total extract of the green microalga Testraselmis suecica. Only the T. suecica extract can completely counteract DPPH-induced injury, since its chemical complexity demonstrated a multilevel protecting and neutralising effect against oxidative stress in PNT2. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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19 pages, 3370 KiB

Open AccessArticle

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

by Christine Vignon, Christelle Debeissat, Jérôme Bourgeais, Nathalie Gallay, Farah Kouzi, Adrienne Anginot, Frédéric Picou, Philippe Guardiola, Elfi Ducrocq, Amélie Foucault, Noémie Ravalet, Louis-Romée Le Nail, Jorge Domenech, Marie-Christine Béné, Marie-Caroline Le Bousse-Kerdilès, Emmanuel Gyan and Olivier Herault

Int. J. Mol. Sci. 2020, 21(22), 8584; https://doi.org/10.3390/ijms21228584 - 14 Nov 2020

Cited by 8 | Viewed by 2959

Abstract

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a [...] Read more.

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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21 pages, 5294 KiB

Open AccessArticle

The Role of Transforming Growth Factor-Beta in Retinal Ganglion Cells with Hyperglycemia and Oxidative Stress

by Hsin-Yi Chen, Yi-Jung Ho, Hsiu-Chuan Chou, En-Chi Liao, Yi-Ting Tsai, Yu-Shan Wei, Li-Hsun Lin, Meng-Wei Lin, Yi-Shiuan Wang, Mei-Lan Ko and Hong-Lin Chan

Int. J. Mol. Sci. 2020, 21(18), 6482; https://doi.org/10.3390/ijms21186482 - 4 Sep 2020

Cited by 26 | Viewed by 3491

Abstract

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-β) is [...] Read more.

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-β) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-β in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-β-related oxidative stress pathway in combination with hydrogen peroxide (H₂O₂). Functional experiments showed that TGF-β1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-β enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-β-mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1α). Summarizing, our results demonstrated that TGF-β keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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12 pages, 4814 KiB

Open AccessArticle

Mangiferin Alleviates Ovalbumin-Induced Allergic Rhinitis via Nrf2/HO-1/NF-κB Signaling Pathways

by Chun Hua Piao, Yan Jing Fan, Thi Van Nguyen, Chang Ho Song and Ok Hee Chai

Int. J. Mol. Sci. 2020, 21(10), 3415; https://doi.org/10.3390/ijms21103415 - 12 May 2020

Cited by 35 | Viewed by 5338

Abstract

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by [...] Read more.

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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Review

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21 pages, 1802 KiB

Open AccessReview

Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives

by Pauline Chazelas, Clara Steichen, Frédéric Favreau, Patrick Trouillas, Patrick Hannaert, Raphaël Thuillier, Sébastien Giraud, Thierry Hauet and Jérôme Guillard

Int. J. Mol. Sci. 2021, 22(5), 2366; https://doi.org/10.3390/ijms22052366 - 27 Feb 2021

Cited by 32 | Viewed by 3864

Abstract

Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production [...] Read more.

Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production and antioxidant defense activity, is a multi-faceted issue, particularly considering the double function of ROS, assuming roles as physiological intracellular signals and as mediators of cellular component damage. Herein, we propose a comprehensive overview of the tools available to explore oxidative stress, particularly in the study of ischemia reperfusion. Applying chemistry as well as biology, we present the different models currently developed to study oxidative stress, spanning the vitro and the silico, discussing the advantages and the drawbacks of each set-up, including the issues relating to the use of in vitro hypoxia as a surrogate for ischemia. Having identified the limitations of historical models, we shall study new paradigms, including the use of stem cell-derived organoids, as a bridge between the in vitro and the in vivo comprising 3D intercellular interactions in vivo and versatile pathway investigations in vitro. We shall conclude this review by distancing ourselves from “wet” biology and reviewing the in silico, computer-based, mathematical modeling, and numerical simulation options: (a) molecular modeling with quantum chemistry and molecular dynamic algorithms, which facilitates the study of molecule-to-molecule interactions, and the integration of a compound in a dynamic environment (the plasma membrane...); (b) integrative systemic models, which can include many facets of complex mechanisms such as oxidative stress or ischemia reperfusion and help to formulate integrated predictions and to enhance understanding of dynamic interaction between pathways. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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16 pages, 778 KiB

Open AccessReview

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

by Sebastien Giraud, Raphaël Thuillier, Jérome Cau and Thierry Hauet

Int. J. Mol. Sci. 2020, 21(21), 8156; https://doi.org/10.3390/ijms21218156 - 31 Oct 2020

Cited by 11 | Viewed by 3883

Abstract

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly [...] Read more.

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation. Full article

(This article belongs to the Special Issue Cellular Models of Oxidative Stress)

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