scholarly journals Relaxin peptides reduce cellular damage in cultured brain slices exposed to transient oxygen–glucose deprivation: an effect mediated by nitric oxide

FACETS ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 118-130
Author(s):  
Nicholas P. DeAdder ◽  
Hannah J. Gillam ◽  
Brian C. Wilson
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Salt Solution ◽  
Cell Damage ◽  
Brain Slices ◽  
The Body ◽  
Cellular Damage ◽  
Separate Experiment ◽  
Ischemia And Reperfusion Injury ◽  
H2 Relaxin

The effect of treatment with human relaxins on cell death was studied in oxygen- and glucose-deprived brain slices. In addition, involvement of nitric oxide and the relaxin receptor, RXFP3, was studied. Brain slices ( n = 12–18/group) were cultured under standard conditions for two weeks and then exposed to: ( i) an oxygenated balanced salt solution, ( ii) a deoxygenated, glucose-free balanced salt solution (OGD media), or ( iii) OGD media containing 10−7 mol/L H2 relaxin, 10−7 mol/L H2 relaxin with 50 μmol/L L-NIL, 10−7 mol/L H3 relaxin, or 10−7 mol/L H3 relaxin with 50 μmol/L L-NIL. Cell death was assessed using propidium iodide fluorescence. In a separate experiment, 10−5 mol/L R3 B1-22R (an antagonist of RXFP3) was added to both H2 and H3 relaxin treatments. H2 and H3 relaxin treatment reduced cell damage or death in OGD slices and L-NIL partially attenuated the effect of H3 relaxin. Antagonism of RXFP3 blocked the effect of H3 but not H2 relaxin. These data increase our understanding of the role of relaxin ligands and their receptors in protecting tissues throughout the body from ischemia and reperfusion injury.

Mechanisms of Nickel-Induced Cell Damage in Allergic Contact Dermatitis and Nutritional Intervention Strategies

2020 ◽  
Vol 20 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
Dana Filatova ◽  
Christine Cherpak
Keyword(s):  
Lipid Peroxidation ◽  
Contact Dermatitis ◽  
Oxidative Damage ◽  
Allergic Contact Dermatitis ◽  
Cell Damage ◽  
Consumer Products ◽  
The Body ◽  
Cellular Damage ◽  
Nutritional Interventions ◽  
Allergic Contact

Background: Hypersensitivity to nickel is a very common cause of allergic contact dermatitis since this metal is largely present in industrial and consumer products as well as in some commonly consumed foods, air, soil, and water. In nickel-sensitized individuals, a cell-mediated delayed hypersensitivity response results in contact to dermatitis due to mucous membranes coming in long-term contact with nickel-containing objects. This process involves the generation of reactive oxidative species and lipid peroxidation-induced oxidative damage. Immunologically, the involvement of T helper (h)-1 and Th-2 cells, as well as the reduced function of T regulatory cells, are of importance. The toxicity, mutagenicity, and carcinogenicity of nickel are attributed to the generation of reactive oxygen species and induction of oxidative damage via lipid peroxidation, which results in DNA damage. Objective: The aim of this research is to identify nutritionally actionable interventions that can intercept nickel-induced cell damage due to their antioxidant capacities. Conclusion: Nutritional interventions may be used to modulate immune dysregulation, thereby intercepting nickel-induced cellular damage. Among these nutritional interventions are a low-nickel diet and an antioxidant-rich diet that is sufficient in iron needed to minimize nickel absorption. These dietary approaches not only reduce the likelihood of nickel toxicity by minimizing nickel exposure but also help prevent oxidative damage by supplying the body with antioxidants that neutralize free radicals.

scholarly journals Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wellington Caio-Silva ◽  
Danielle da Silva Dias ◽  
Carolina Victoria Cruz Junho ◽  
Karine Panico ◽  
Raquel Silva Neres-Santos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Redox Balance ◽  
Renal Ischemia ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Inflammatory Conditions

In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.

l-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction

2006 ◽  
Vol 290 (2) ◽  
pp. F357-F363 ◽  
Author(s):  
William Conners ◽  
Catherine Whitebeck ◽  
Paul Chicester ◽  
Robert Legget ◽  
Alpha Dian-Yu Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Contractile Function ◽  
Outlet Obstruction ◽  
Cellular Damage ◽  
Ischemia And Reperfusion Injury ◽  
Free Radical Damage ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur and the role that nitric oxide may play in its pathophysiology. Surgical PBOO (1, 3, and 7 days) were performed on male New Zealand White rabbits. Half of the animals were premedicated for 3 days with NG-nitro-l-arginine methyl ester(l-NAME), an inhibitor of nitric oxide synthase before obstruction. Bladder weight increased with duration of PBOO but was significantly lower at 3 and 7 days in animals treated with l-NAME compared with their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1 day postobstruction, bladder contractility was significantly lower in the l-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the l-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day after obstruction was significantly higher in the l-NAME-treated animals than in the untreated controls but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the l-NAME-treated animals at 3 and especially at 7 days. Nerve density decreased progressively after obstruction; however, it decreased to a significantly lesser degree in the l-NAME-treated bladders than in the untreated groups. These results suggest that l-NAME pretreatment enhanced ischemic damage at 1 day after obstruction but protected the bladder from nitric oxide-generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.

scholarly journals Nitric oxide mediates hepatocyte injury

1998 ◽  
Vol 275 (5) ◽  
pp. G1117-G1126 ◽  
Author(s):  
Jiang Huai Wang ◽  
H. Paul Redmond ◽  
Qiong Di Wu ◽  
David Bouchier-Hayes
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Cell Damage ◽  
Acute Hepatic Failure ◽  
Severe Trauma ◽  
No Production ◽  
Enzyme Release ◽  
Oxygen Intermediates ◽  
No Donor ◽  
Tnf Α

The degree of acute hepatic failure after severe trauma and sepsis is related to the extent of hepatocyte (HC) damage and cell death resulting from either necrosis or apoptosis. We have previously demonstrated that tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) can directly lead to HC necrosis, but not apoptosis. To date, the reactive oxygen intermediates (ROI) and nitric oxide (NO) have been shown to play a potential role in the induction of cell apoptosis. However, it is unknown whether ROI and NO are involved in HC cell death. Therefore, in this study we tested the hypothesis that NO and ROI exert different effects on HC cell death. TNF-α and LPS alone failed to induce HC apoptosis but when combined with antioxidants resulted in HC apoptosis and DNA fragmentation, which is correlated with an increase in NO production. This effect was attenuated by the NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA). Moreover, the NO donor sodium nitroprusside resulted in HC apoptosis and cell damage as represented by hepatocellular enzyme release. Antioxidants inhibited TNF-α- and LPS-mediated ROI generation and peroxynitrite formation in HC. TNF-α- and LPS-induced HC damage could be further reduced by the combination of antioxidants andl-NMMA. These results indicate that NO is involved in HC injury, primarily through the induction of HC apoptosis.

scholarly journals Current Mechanistic Concepts in Ischemia and Reperfusion Injury

2018 ◽  
Vol 46 (4) ◽  
pp. 1650-1667 ◽  
Author(s):  
Meng-Yu Wu ◽  
Giou-Teng Yiang ◽  
Wan-Ting Liao ◽  
Andy Po-Yi Tsai ◽  
Yeung-Leung Cheng ◽  
...  
Keyword(s):  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Medical Condition ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Clinical Manifestations ◽  
Multiple Organ ◽  
Ischemia And Reperfusion Injury ◽  
Oxidase System

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

scholarly journals tBHQ Induces a Hormetic Response That Protects L6 Myoblasts against the Toxic Effect of Palmitate

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Pedro Posadas-Rodríguez ◽  
Natalia Esmeralda Posadas-Rodríguez ◽  
Viridiana Yazmín González-Puertos ◽  
Rafael Toledo-Pérez ◽  
José Luis Ventura-Gallegos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Cell Death ◽  
Toxic Effect ◽  
Acid Synthesis ◽  
Overweight And Obesity ◽  
The Body ◽  
Cellular Damage ◽  
Sodium Palmitate ◽  
Hormetic Response

Nutritional status, in particular overweight and obesity, as well as sedentarism and high-fat diet consumption, are important risk factors to develop chronic diseases, which have a higher impact on the elderly’s health. Therefore, these nutritional problems have become a concern to human healthspan and longevity. The fatty acids obtained thru the diet or due to fatty acid synthesis during obesity accumulate within the body generating toxicity and cell death. Fat is not only stored in adipose tissue, but it can also be stored in skeletal muscle. Palmitic acid (PA) has been reported as one of the most important saturated free fatty acids; it is associated to chronic oxidative stress and increased mitochondrial ROS production causing cell death by apoptosis. In skeletal muscle, palmitate has been associated with various pathophysiological consequences, which lead to muscle deterioration during aging and obesity. Since molecules that modify redox state have been proven to prevent cellular damage by inducing a hormetic response, the aim of this study was to evaluate if tert-butylhydroquinone (tBHQ) could activate an antioxidant hormetic response that would be able to protect L6 myoblasts from palmitate toxic effect. Our results provide evidence that tBHQ is able to protect L6 myoblasts against the toxicity induced by sodium palmitate due to a synergistic activation of different signaling pathways such as Nrf2 and NF-κB.

Alpha-Tocopherol Protects Cultured Human Cells from the Acute Lethal Cytotoxicity of Dioxin

2002 ◽  
Vol 72 (3) ◽  
pp. 147-153 ◽  
Author(s):  
Kei-Ichi Hirai ◽  
Jie-Hong Pan ◽  
Ying-Bo Shui ◽  
Eriko Simamura ◽  
Hiroki Shimada ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Damage ◽  
Smooth Endoplasmic Reticulum ◽  
Dehydroascorbic Acid ◽  
Human Cells ◽  
Alpha Tocopherol ◽  
Cervical Cancer Cells ◽  
Cultured Human Cells ◽  
Nuclear Damage ◽  
Conjunctival Epithelial Cells

The possible protection of cultured human cells from acute dioxin injury by antioxidants was investigated. The most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), caused vacuolization of the smooth endoplasmic reticulum and Golgi apparatus in cultured human conjunctival epithelial cells and cervical cancer cells. Subsequent nuclear damage included a deep irregular indentation resulting in cell death. A dosage of 30–40 ng/mL TCDD induced maximal intracellular production of H2O2 at 30 minutes and led to severe cell death (0–31% survival) at two hours. A dose of 1.7 mM alpha-tocopherol or 1 mM L-dehydroascorbic acid significantly protected human cells against acute TCDD injuries (78–97% survivals), but vitamin C did not provide this protection. These results indicate that accidental exposure to fatal doses of TCDD causes cytoplasmic free radical production within the smooth endoplasmic reticular systems, resulting in severe cytotoxicity, and that vitamin E and dehydroascorbic acid can protect against TCDD-induced cell damage.

Apoptotic cell death triggered by nitric oxide in pancreatic beta-cells

Diabetes ◽  
1995 ◽  
Vol 44 (7) ◽  
pp. 733-738 ◽  
Author(s):  
H. Kaneto ◽  
J. Fujii ◽  
H. G. Seo ◽  
K. Suzuki ◽  
T. Matsuoka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

Chronic Hypoxia as a Potential Factor in Human Life-threatening Diseases

2017 ◽  
Vol 10 (4) ◽  
pp. 3759-3762
Author(s):  
Sandhya MNVS ◽  
Vanitha K ◽  
Ramesh A
Keyword(s):  
Chronic Hypoxia ◽  
Atmospheric Oxygen ◽  
Human Life ◽  
The Body ◽  
Cellular Damage ◽  
Otto Warburg ◽  
Regular Treatment ◽  
Breathing Exercises ◽  
Hypoxic Conditions ◽  
Cancerous Cell

The review article focuses on the importance of adequate oxygen levels in the body as cure and therapy for many ailments. It is known that hypoxia is the cause for cellular damage and if it can be applied to major patho-physiology’s, it can be observed that slow and chronic hypoxic conditions are the cause for most of the diseases. On the contrary, providing each cell of the body with proper oxygen may be helpful in maintaining the immunity of the body and therefore treating many disease conditions. This theory, if tested may show positive results in heart related diseases, neuronal disorders, stresses, digestive disorders and the unresolved cancer too. Slow decrease in the levels of atmospheric oxygen could be a reason to induce chronic hypoxia. According to Dr. Otto Warburg, a Noble laurate, a normal cell when deprived of oxygen, may get converted to a cancerous cell, whereas a cancerous cell cannot survive in aerobic conditions. If this part of his research be concentrated on, there could be fruitful results in the treatment of cancer. To maintain adequate levels of oxygen in the body, simple yogic breathing practices are helpful. And to maintain the adequate atmospheric oxygen, trees and plants which cleanse the atmospheric air are useful. Clinical surveys on volunteers who have been practicing regular breathing exercises can prove the fact that proper and concentrated respiration could prevent many diseases. Thus, supplementing breathing exercises along with the regular treatment for cancer patients could be helpful in alleviating cancer and other diseases.

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