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Oxidative stress

About: Oxidative stress is a research topic. Over the lifetime, 86513 publications have been published within this topic receiving 3845790 citations. The topic is also known as: oxydative stress.


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Journal ArticleDOI
TL;DR: The role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease are discussed.
Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD. Increased production of reactive oxygen species (ROS) associated with age- and disease-dependent loss of mitochondrial function, altered metal homeostasis, and reduced antioxidant defense directly affect synaptic activity and neurotransmission in neurons leading to cognitive dysfunction. In addition, molecular targets affected by ROS include nuclear and mitochondrial DNA, lipids, proteins, calcium homeostasis, mitochondrial dynamics and function, cellular architecture, receptor trafficking and endocytosis, and energy homeostasis. Abnormal cellular metabolism in turn could affect the production and accumulation of amyloid-β (Aβ) and hyperphosphorylated Tau protein, which independently could exacerbate mitochondrial dysfunction and ROS production, thereby contributing to a vicious cycle. While mounting evidence implicates ROS in the AD etiology, clinical trials with antioxidant therapies have not produced consistent results. In this review, we will discuss the role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease.

967 citations

Journal ArticleDOI
TL;DR: The results suggest that intratracheal instillation of ultrafine TiO(2) particles may cause an inflammatory response.

966 citations

Journal ArticleDOI
TL;DR: The comparative analysis demonstrated that particle composition probably played a primary role in the cytotoxic effects of different nanoparticles, however, the potential genotoxicity might be mostly attributed to particle shape.
Abstract: Although the biological effects of some nanomaterials have already been assessed, information on toxicity and possible mechanisms of various particle types are insufficient. Moreover, the role of particle properties in the toxic reaction remains to be fully understood. In this paper, we aimed to explore the interrelationship between particle size, shape, chemical composition and toxicological effects of four typical nanomaterials with comparable properties: carbon black (CB), single wall carbon nanotube, silicon dioxide (SiO(2)) and zinc dioxide (ZnO) nanoparticles. We investigated the cytotoxicity, genotoxicity and oxidative effects of particles on primary mouse embryo fibroblast cells. As observed in the methyl thiazolyl tetrazolium (MTT) and water-soluble tetrazolium (WST) assays, ZnO induced much greater cytotoxicity than non-metal nanoparticles. This was significantly in accordance with intracellular oxidative stress levels measured by glutathione depletion, malondialdehyde production, superoxide dismutase inhibition as well as reactive oxygen species generation. The results indicated that oxidative stress may be a key route in inducing the cytotoxicity of nanoparticles. Compared with ZnO nanoparticles, carbon nanotubes were moderately cytotoxic but induced more DNA damage determined by the comet assay. CB and SiO(2) seemed to be less effective. The comparative analysis demonstrated that particle composition probably played a primary role in the cytotoxic effects of different nanoparticles. However, the potential genotoxicity might be mostly attributed to particle shape.

963 citations

Journal ArticleDOI
TL;DR: It is demonstrated that oxidative stress is sensed and transduced by glutathione peroxidase 4 (GPx4) into a-yet-unrecognized cell-death pathway, and the identified pathway reveals promising targets for future therapies.

962 citations

Journal ArticleDOI
TL;DR: Reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix.
Abstract: Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.

961 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20242
20238,839
202217,614
20216,457
20206,203
20195,669