670nm Photobiomodulation Modulates Bioenergetics And Oxidative Stress, Decreasing Inflammatory Mediator Production In An In Vitro Model Of Diabetic Retinopathy

Abstract Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-kB (NFkB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Current therapies are invasive, frequently ineffective, and have adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will dimish oxidative stress preventing downstream inflammatory mechanisms associated with DR. We used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished ROS production and preserved mitochondrial integrity and ATP production in this in vitro model of diabetic retinopathy. Furthermore, treatment for 3 days in culture reduced NFkB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this established DR model system suggests light treatment could become an early therapeutic option for DR.

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670nm photobiomodulation modulates bioenergetics and oxidative stress, in rat Müller cells challenged with high glucose

PLoS ONE ◽

10.1371/journal.pone.0260968 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260968

Author(s):

Hannah J. Nonarath ◽

Alexandria E. Hall ◽

Gopika SenthilKumar ◽

Betsy Abroe ◽

Janis T. Eells ◽

...

Keyword(s):

Oxidative Stress ◽

Glial Cells ◽

High Glucose ◽

Near Infrared ◽

Müller Cells ◽

Model System ◽

Light Treatment ◽

Muller Cells ◽

Müller Glial Cells

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-κB (NFκB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Muller glial cells, spanning the entirety of the retina, are involved in DR inflammation. Mitigation of DR pathology currently occurs via invasive, frequently ineffective therapies which can cause adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will diminish oxidative stress preventing downstream inflammatory mechanisms associated with DR initiated by Muller cells. In this study, we used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished reactive oxygen species (ROS) production and preserved mitochondrial integrity in this in vitro model of early DR. Furthermore, treatment for 3 days in culture reduced NFκB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this in vitro high glucose model system suggests light treatment could mitigate early deleterious effects modulating inflammatory signaling and diminishing oxidative stress.

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Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

Current Pharmaceutical Design ◽

10.2174/1381612826666200408101550 ◽

2020 ◽

Vol 26 (22) ◽

pp. 2610-2619 ◽

Cited By ~ 2

Author(s):

Tarique Hussain ◽

Ghulam Murtaza ◽

Huansheng Yang ◽

Muhammad S. Kalhoro ◽

Dildar H. Kalhoro

Keyword(s):

Oxidative Stress ◽

Chronic Diseases ◽

Inflammatory Diseases ◽

Therapeutic Option ◽

Cellular Level ◽

Antiinflammatory Drugs ◽

Suitable Alternative ◽

Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

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Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

10.21203/rs.3.rs-57664/v1 ◽

2020 ◽

Author(s):

Isabel Karkossa ◽

Anne Bannuscher ◽

Bryan Hellack ◽

Wendel Wohlleben ◽

Julie Laloy ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Alveolar Macrophages ◽

Model System ◽

Alveolar Epithelial Cells ◽

Model Systems ◽

Alveolar Epithelial ◽

Different Levels

Abstract Background The immense variety and constant development of nanomaterials (NMs) raise the demand for a facilitated risk assessment, for which knowledge on NMs mode of actions (MoAs) is required. For this purpose, a comprehensive data basis is of paramountcy that can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is indispensable to follow the 3R concept and to master the high number of NMs. In the present study, we aimed at comparing NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data evaluation strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For in vitro investigations, alveolar epithelial cells and alveolar macrophages were treated with different doses of NMs, and the results were compared to effects on rat lungs after short-term inhalations and instillations at varying doses with and without a recovery period.Results Since the production of reactive oxygen species (ROS) is described to be a critical biological effect of NMs, and enrichment analyses confirmed oxidative stress as a significant effect upon NM treatment in vitro in the present study, we focused on different levels of oxidative stress. Thus, we found opposite changes for proteins and metabolites that are related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, illustrating that NMs MoAs depend on the used model system. Interestingly, in vivo, pathways related to inflammation were affected to a greater extent than oxidative stress responses. Hence, the assignment of the observed effects to the levels of oxidative stress was different in vitro and in vivo as well. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo.Conclusions The consistent classification indicates both tested cell lines to be suitable for NM toxicity assessment even though the induced levels of oxidative stress strongly depend on the used model systems. Thus, the here presented results highlight that model systems need to be carefully revised to decipher the extent to which they can replace in vivo testing.

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Experimental and Clinical Applications of Red and Near-Infrared Photobiomodulation on Endothelial Dysfunction: A Review

Biomedicines ◽

10.3390/biomedicines9030274 ◽

2021 ◽

Vol 9 (3) ◽

pp. 274 ◽

Cited By ~ 1

Author(s):

Esteban Colombo ◽

Antonio Signore ◽

Stefano Aicardi ◽

Angelina Zekiy ◽

Anatoliy Utyuzh ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Near Infrared ◽

Disease Risk ◽

In Vivo Studies ◽

Infrared Light ◽

Animal Cells ◽

Atp Production ◽

Main Regulator

Background: Under physiological conditions, endothelial cells are the main regulator of arterial tone homeostasis and vascular growth, sensing and transducing signals between tissue and blood. Disease risk factors can lead to their unbalanced homeostasis, known as endothelial dysfunction. Red and near-infrared light can interact with animal cells and modulate their metabolism upon interaction with mitochondria’s cytochromes, which leads to increased oxygen consumption, ATP production and ROS, as well as to regulate NO release and intracellular Ca2+ concentration. This medical subject is known as photobiomodulation (PBM). We present a review of the literature on the in vitro and in vivo effects of PBM on endothelial dysfunction. Methods: A search strategy was developed consistent with the PRISMA statement. The PubMed, Scopus, Cochrane, and Scholar electronic databases were consulted to search for in vitro and in vivo studies. Results: Fifty out of >12,000 articles were selected. Conclusions: The PBM can modulate endothelial dysfunction, improving inflammation, angiogenesis, and vasodilatation. Among the studies, 808 nm and 18 J (0.2 W, 2.05 cm2) intracoronary irradiation can prevent restenosis as well as 645 nm and 20 J (0.25 W, 2 cm2) can stimulate angiogenesis. PBM can also support hypertension cure. However, more extensive randomised controlled trials are necessary.

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Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

10.21203/rs.3.rs-57664/v2 ◽

2021 ◽

Author(s):

Isabel Karkossa ◽

Anne Bannuscher ◽

Bryan Hellack ◽

Wendel Wohlleben ◽

Julie Laloy ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Alveolar Macrophages ◽

Model System ◽

Alveolar Epithelial Cells ◽

Model Systems ◽

Alveolar Epithelial ◽

Different Levels

Abstract Background: The immense variety and constant development of nanomaterials (NMs) raise the demand for a facilitated risk assessment, for which knowledge on NMs mode of actions (MoAs) is required. For this purpose, a comprehensive data basis is of paramountcy that can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is indispensable to follow the 3R concept and to master the high number of NMs. In the present study, we aimed at comparing NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data evaluation strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For in vitro investigations, rat alveolar epithelial cells (RLE-6TN) and rat alveolar macrophages (NR8383) were treated with different doses of NMs, and the results were compared to effects on rat lungs after short-term inhalations and instillations at varying doses with and without a recovery period.Results: Since the production of reactive oxygen species (ROS) is described to be a critical biological effect of NMs, and enrichment analyses confirmed oxidative stress as a significant effect upon NM treatment in vitro in the present study, we focused on different levels of oxidative stress. Thus, we found opposite changes for proteins and metabolites that are related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, illustrating that NMs MoAs depend on the used model system. Interestingly, in vivo, pathways related to inflammation were affected to a greater extent than oxidative stress responses. Hence, the assignment of the observed effects to the levels of oxidative stress was different in vitro and in vivo as well. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo.Conclusions: The consistent classification indicates both tested cell lines to be suitable for NM toxicity assessment even though the induced levels of oxidative stress strongly depend on the used model systems. Thus, the here presented results highlight that model systems need to be carefully revised to decipher the extent to which they can replace in vivo testing.

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Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway

BMC Ophthalmology ◽

10.1186/s12886-021-02215-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mengdan Yu ◽

Lijun Zhang ◽

Shasha Sun ◽

Zhenhua Zhang

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Necrosis Factor Alpha ◽

Retinal Injury ◽

Anti Oxidant ◽

Related Enzyme ◽

Anti Inflammatory ◽

And Oxidative Stress

Abstract Background Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR. Methods High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting. Results GLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo. Conclusion GLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.

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Comparative phytochemical analysis of Phlogacanthus thyrsiflorus Nees: Implications on attenuation of pro-oxidants and pathogen virulence in Caenorhabditis elegans model system

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i5.17319 ◽

2017 ◽

Vol 10 (5) ◽

pp. 361

Author(s):

Kitlangki Suchiang ◽

Nitasha H Kayde

Keyword(s):

Oxidative Stress ◽

Free Radicals ◽

Free Radical ◽

Caenorhabditis Elegans ◽

Model System ◽

Wild Type ◽

C Elegans ◽

Mutant Strains

Background: Phlogacanthus thyrsiflorus Nees (P. thyrsiflorus) of Acanthaceae family is endogenous to sub-tropical Himalayas. It has been reported to be used traditionally in Jaintia tribe of Meghalaya, India for treatment of many ailments.Objectives: The aim was to detect the active compounds present in the leaves for evaluation of in vitro free radicals scavenging potentials. Leaves protective actions in vivo will be investigated using Caenorhabditis elegans (C. elegans) model system utilizing wild type and mutant strains and the phenomena of host-pathogens interactions.Materials and methods: Gas chromatography/ Mass spectrometry (GC/MS) was used for detection of different compounds present. The versatility of leaf extracts to scavenge different free radicals generated in vitro was assessed with different in vitro methods. Survival analysis of wild type and mutant strains C. elegans under enhanced pro-oxidants exposure was investigated in vivo. Fast killing assay was also performed to study the extracts modulatory activity on host C. elegans survival under pathogen Pseudomonas aeruginosa infection.Results: Forty compounds were detected in methanolic fraction of the extract with variable percentages. Both aqueous and methanol extract possessed remarkable, versatile free radical scavenging activity irrespective of the types of free radical generated. The in vivo experiments are in compliance, with observable increased survival ability percentage of C. elegans under intense exogenous oxidative stress and pathogen infection.Conclusion: Our findings enlightened the different compounds present with versatility of P. thyrsiflorus in tackling different free radicals generated both in vitro and in vivo that highly support for its candidature as a good antioxidant source. Our findings may justify the historical relevance of this plant in herbal remedies that could form the basis for inquiry of new active principles.Keywords: Free radicals, Oxidative stress, Caenorhabditis elegans, Phlogacanthus thyrsiflorus, Phytochemicals

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Aldosterone Excess Induced Mitochondria Decrease and Dysfunction via Mineralocorticoid Receptor and Oxidative Stress In Vitro and In Vivo

Biomedicines ◽

10.3390/biomedicines9080946 ◽

2021 ◽

Vol 9 (8) ◽

pp. 946

Author(s):

Cheng-Hsuan Tsai ◽

Chien-Ting Pan ◽

Yi-Yao Chang ◽

Shih-Yuan Peng ◽

Po-Chin Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dna ◽

Mitochondrial Dysfunction ◽

Mineralocorticoid Receptor ◽

Cardiac Mitochondria ◽

Mice Model ◽

Atp Production ◽

And Oxidative Stress

Aldosterone excess plays a major role in the progression of cardiac dysfunction and remodeling in clinical diseases such as primary aldosteronism and heart failure. However, the effect of aldosterone excess on cardiac mitochondria is unclear. In this study, we investigated the effect of aldosterone excess on cardiac mitochondrial dysfunction and its mechanisms in vitro and in vivo. We used H9c2 cardiomyocytes to investigate the effect and mechanism of aldosterone excess on cardiac mitochondria, and further investigated them in an aldosterone-infused ICR mice model. The results of the cell study showed that aldosterone excess decreased mitochondrial DNA, COX IV and SOD2 protein expressions, and mitochondria ATP production. These effects were abolished or attenuated by treatment with a mineralocorticoid receptor (MR) antagonist and antioxidant. With regard to the signal transduction pathway, aldosterone suppressed cardiac mitochondria through an MR/MAPK/p38/reactive oxygen species pathway. In the mouse model, aldosterone infusion decreased the amount of cardiac mitochondrial DNA and COX IV protein, and the effects were also attenuated by treatment with an MR antagonist and antioxidant. In conclusion, aldosterone excess induced a decrease in mitochondria and mitochondrial dysfunction via MRs and oxidative stress in vitro and in vivo.

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pH-Sensitive and Long-Circulation Nanoparticles for Near-Infrared Fluorescence Imaging-Monitored and Chemo-Photothermal Synergistic Treatment Against Gastric Cancer

Frontiers in Pharmacology ◽

10.3389/fphar.2020.610883 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yun Zhou ◽

Xuanzi Sun ◽

Liansuo Zhou ◽

Xiaozhi Zhang

Keyword(s):

Gastric Cancer ◽

Near Infrared ◽

Therapeutic Option ◽

Drug Loading ◽

Gastric Cancer Cell Line ◽

Postoperative Treatment ◽

Maximum Temperature ◽

Hydrodynamic Diameter

Gastrectomy is the primary therapeutic option for gastric cancer. Postoperative treatment also plays a crucial role. The strategy to improve the postoperative prognosis of gastric cancer requires a combined system that includes a more efficient synergistic treatment and real-time monitoring after surgery. In this study, photothermal-chemotherapy combined nanoparticles (PCC NPs) were prepared via π-π stacking to perform chemo-photothermal synergistic therapy and continuous imaging of gastric cancer. PCC NPs had a spherical morphology and good monodispersity under aqueous conditions. The hydrodynamic diameter of PCC NPs was 59.4 ± 3.6 nm. PCC NPs possessed strong encapsulation ability, and the maximum drug loading rate was approximately 37%. The NPs exhibited extraordinary stability and pH-response release profiles. The NPs were rapidly heated under irradiation. The maximum temperature was close to 58°C. PCC NPs showed good biocompatibility both in vitro and in vivo. Moreover, the NPs could effectively be used for in vivo continuous monitoring of gastric cancer. After one injection, the fluorescent signal remained in tumor tissues for nearly a week. The inhibitory effect of PCC NPs was evaluated in a gastric cancer cell line and xenograft mouse model. Both in vitro and in vivo evaluations demonstrated that PCC NPs could be used for chemo-photothermal synergistic therapy. The suppression effect of PCC NPs was significantly better than that of single chemotherapy or photothermal treatment. This study lays the foundation for the development of novel postoperative treatments for gastric cancer.

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