scholarly journals The Role of Reactive Oxygen Species in the Pathogenesis of Adipocyte Dysfunction in Metabolic Syndrome. Prospects of Pharmacological Correction

2017 ◽  
Vol 72 (1) ◽  
pp. 11-16 ◽  
Author(s):  
E. S. Prokudina ◽  
L. N. Maslov ◽  
V. V. Ivanov ◽  
I. D. Bespalova ◽  
D. S. Pismennyi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Positive Impact ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tnf Α ◽  
The One

It is established that oxidative stress induces insulin resistance of adipocytes, increases secretion leptin, IL-6, TNF-α by adipocytes. Adiponectin secretion by adipocytes is reduced after the action of reactive oxygen species. Metabolic syndrome contributes to oxidative stress in adipose tissue, on the one hand due to the activation of production of reactive oxygen species by adipocyte NADPH-oxidase, and on the other hand by reducing the antioxidant defense adipocytes. It is found that obesity itself can induce oxidative stress. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α play an important role in the pathogenesis of oxidative stress of adipocytes. Metformin remains the cure for the treatment of insulin resistance. The positive results in the treatment of metabolic syndrome by losartan were obtained. Antioxidants and flavonoids exhibit a positive impact on the course of the experimental metabolic syndrome.

scholarly journals The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

2010 ◽  
Vol 63 (11-12) ◽  
pp. 827-832 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic ◽  
Rada Jesic-Vukicevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Severe Liver ◽  
Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Gokhan Zengin ◽  
Sukhbir Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ionizing Radiation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Radiation Induced ◽  
Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

scholarly journals PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Sergio Rius-Pérez ◽  
Isabel Torres-Cuevas ◽  
Iván Millán ◽  
Ángel L. Ortega ◽  
Salvador Pérez
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Inflammatory Response ◽  
Reactive Oxygen ◽  
High Energy ◽  
Low Grade ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Integrative View

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells

2006 ◽  
Vol 291 (5) ◽  
pp. C897-C908 ◽  
Author(s):  
Shyamali Basuroy ◽  
Sujoy Bhattacharya ◽  
Dilyara Tcheranova ◽  
Yan Qu ◽  
Raymond F. Regan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Serum Deprivation ◽  
Oxygen Species ◽  
Tnf Α ◽  
Endogenous Protection ◽  
Cerebral Vascular

Tumor necrosis factor-α (TNF-α) causes oxidative stress and apoptosis in a variety of cell types. Heme oxygenase (HO) degrades heme to bilirubin, an antioxidant, and carbon monoxide (CO), a cell cycle modulator, and a vasodilator. Newborn pig cerebral microvascular endothelial cells (CMVEC) highly express constitutive HO-2. We investigated the role of HO-2 in protection against TNF-α-induced apoptosis in cerebral vascular endothelium. In CMVEC from mice and newborn pigs, 15 ng/ml TNF-α alone, or with 10 μg/ml cycloheximide (CHX) caused apoptosis detected by nuclear translocation of p65 NF-κB, caspase-3 activation, DNA fragmentation, cell-cell contact destabilization, and cell detachment. TNF-α did not induce HO-1 expression in CMVEC. CMVEC from HO-2 knockout mice showed greater sensitivity to apoptosis caused by serum deprivation and TNF-α than did wild-type mice. TNF-α increased reactive oxygen species generation, including hydrogen peroxide and superoxide radicals, as detected by dihydrorhodamine-123 and dihydroethidium. The TNF-α response was inhibited by superoxide dismutase and catalase suggesting apoptosis is oxidative stress related. Inhibition of endogenous HO-2 in newborn pig CMVEC increased oxidative stress and exaggerated apoptosis caused by serum deprivation and TNF-α. In HO-1-overexpressing CMVEC (HO-1 selective induction by cobalt portophyrin), TNF-α did not cause apoptosis. A CO-releasing compound, CORM-A1, and bilirubin blocked TNF-α-induced reactive oxygen species accumulation and apoptosis consistent with the antioxidant and antiapoptotic roles of the end products of HO activity. We conclude that HO-2 is critical for protection of cerebrovascular endothelium against apoptotic changes induced by oxidative stress and cytokine-mediated inflammation.

Role of Reactive Oxygen Species and Bcl-2 Family Proteins in TNF-α-Induced Apoptosis of Lymphocytes

2010 ◽  
Vol 149 (2) ◽  
pp. 180-183 ◽  
Author(s):  
N. V. Ryazanceva ◽  
V. V. Novickiy ◽  
O. B. Zhukova ◽  
A. K. Biktasova ◽  
O. E. Chechina ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals The role of oxidative stress in alcoholic liver injury

2009 ◽  
Vol 62 (11-12) ◽  
pp. 547-553 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Alcoholic Liver Injury ◽  
Chronic Ethanol Consumption

Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and ?-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

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