Glutamatergic Dysbalance and Oxidative Stress in In Vivo and In Vitro Models of Psychosis Based on Chronic NMDA Receptor Antagonism

Silver nanoparticles (AgNPs) are being employed in numerous consumer goods and applications; however, they are renowned for inducing negative cellular consequences including toxicity, oxidative stress, and an inflammatory response. Nanotoxicological outcomes are dependent on numerous factors, including physicochemical, biological, and environmental influences. Currently, NP safety evaluations are carried out in both cell-based in vitro and animal in vivo models, with poor correlation between these mechanisms. These discrepancies highlight the need for enhanced exposure environments, which retain the advantages of in vitro models but incorporate critical in vivo influences, such as fluid dynamics. This study characterized the effects of dynamic flow on AgNP behavior, cellular interactions, and oxidative stress within both adherent alveolar (A549) and suspension monocyte (U937) models. This study determined that the presence of physiologically relevant flow resulted in substantial modifications to AgNP cellular interactions and subsequent oxidative stress, as assessed via reactive oxygen species (ROS), glutathione levels, p53, NFκB, and secretion of pro-inflammatory cytokines. Within the adherent model, dynamic flow reduced AgNP deposition and oxidative stress markers by roughly 20%. However, due to increased frequency of contact, the suspension U937 cells were associated with higher NP interactions and intracellular stress under fluid flow exposure conditions. For example, the increased AgNP association resulted in a 50% increase in intracellular ROS and p53 levels. This work highlights the potential of modified in vitro systems to improve analysis of AgNP dosimetry and safety evaluations, including oxidative stress assessments.

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Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Cell Death and Disease ◽

10.1038/s41419-020-03260-9 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Xiaozhong Huang ◽

Yujuan Shi ◽

Hongjin Chen ◽

Rongrong Le ◽

Xiaohua Gong ◽

...

Keyword(s):

Oxidative Stress ◽

In Vitro Models ◽

Sirtuin 1 ◽

Health Concern ◽

Flavonoid Compound ◽

Direct Binding ◽

And Oxidative Stress

AbstractDiabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.

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Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽

10.3390/antiox10040507 ◽

2021 ◽

Vol 10 (4) ◽

pp. 507

Author(s):

Rosaria Meccariello ◽

Stefania D’Angelo

Keyword(s):

Oxidative Stress ◽

Food Sources ◽

Preventive Action ◽

Nutritional Interventions ◽

Beneficial Effects ◽

Age Related ◽

Macromolecular Damage ◽

And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

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Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

International Immunopharmacology ◽

10.1016/j.intimp.2021.107593 ◽

2021 ◽

Vol 96 ◽

pp. 107593

Author(s):

Yiming Ma ◽

Lijuan Luo ◽

Xiangming Liu ◽

Herui Li ◽

Zihang Zeng ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

And Oxidative Stress

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Oxygen and Oxidative Stress Modulate the Expression of Uncoupling Protein-5 in Vitro and in Vivo

Advances in Experimental Medicine and Biology - Oxygen Transport to Tissue XXV ◽

10.1007/978-1-4757-6125-2_15 ◽

2003 ◽

pp. 103-107 ◽

Cited By ~ 9

Author(s):

Paola Pichiule ◽

Juan C. Chavez ◽

Joseph C. LaManna

Keyword(s):

Oxidative Stress ◽

Uncoupling Protein ◽

And Oxidative Stress

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Evidence of Autophagy Gene and Protein Expression Response to Heat and Oxidative Stress in Avian Muscle Cells: In Vivo and in Vitro Studies.

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2014.10.352 ◽

2014 ◽

Vol 76 ◽

pp. S72

Author(s):

Sami Dridi ◽

Alissa Piekarski ◽

Kentu Lassiter ◽

Elizabeth Greene ◽

Nick Anthony ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Muscle Cells ◽

Autophagy Gene ◽

Avian Muscle ◽

Gene And Protein Expression ◽

Expression Response ◽

And Oxidative Stress

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Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

International Journal of Molecular Sciences ◽

10.3390/ijms221910822 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10822

Author(s):

Agata Winiarska ◽

Monika Knysak ◽

Katarzyna Nabrdalik ◽

Janusz Gumprecht ◽

Tomasz Stompór

Keyword(s):

Oxidative Stress ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Kidney Injury ◽

Organ Protection ◽

In Vivo Models ◽

Diabetic Kidney ◽

And Oxidative Stress

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) antagonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R antagonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.

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The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect

AJP Renal Physiology ◽

10.1152/ajprenal.00297.2018 ◽

2019 ◽

Vol 317 (4) ◽

pp. F881-F889 ◽

Cited By ~ 7

Author(s):

Hyung Jung Oh ◽

Hyewon Oh ◽

Bo Young Nam ◽

Je Sung You ◽

Dong-Ryeol Ryu ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Injury ◽

Antioxidative Effect ◽

In Vivo Experiments ◽

Apoptotic Markers ◽

Cytoplasmic Vacuoles ◽

Transmission Electron ◽

And Oxidative Stress

As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.

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In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

Toxicology Research ◽

10.1093/toxres/tfaa078 ◽

2020 ◽

Vol 9 (6) ◽

pp. 734-740

Author(s):

Yigit Sezer ◽

Ayse Tarbin Jannuzzi ◽

Marilyn A Huestis ◽

Buket Alpertunga

Keyword(s):

Oxidative Stress ◽

Neuronal Cells ◽

Underlying Mechanism ◽

Synthetic Cannabinoid ◽

Stress Effects ◽

Legal High ◽

New Generation ◽

And Oxidative Stress

Abstract Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

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Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo

Clinical Science ◽

10.1042/cs20190331 ◽

2019 ◽

Vol 133 (13) ◽

pp. 1523-1536 ◽

Cited By ~ 8

Author(s):

Xiao Sun ◽

Xiuli Feng ◽

Dandan Zheng ◽

Ang Li ◽

Chunyan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Cordyceps Sinensis ◽

Chronic Obstructive ◽

Therapeutic Effects ◽

Related Proteins ◽

And Oxidative Stress

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

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