Pathogenesis of Mood Disorders
Dr. Ather Muneer in Mood Disorders, 2018
Mounting evidence from clinical and preclinical studies incriminates inflammation as a critical mediator in the pathophysiology of mood disorders. Indeed, elevated levels of proinflammatory cytokines have been repeatedly demonstrated in both major depressive disorder and bipolar disorder. Among psychiatric diseases, mood disorders are exclusive in presentation as these patients vacillate between two opposite mood states; that is, mania and depression. During acute affective episodes, patients have elevated levels of inflammatory proteins, i.e., cytokines and chemokines, in the peripheral circulation and this abnormality is well documented in both major depressive disorder and bipolar disorder. The activated microglia intensify the inflammatory response by releasing reactive oxygen species, reactive nitrogen species, cytokines and chemokines. It is now known that repeated and severe stressors, in the absence of pathogenic disease, can induce an inflammatory response and this has been aptly called the "sterile inflammation".
Atmospheric Oxidants and Respiratory Tract Surfaces
Jürgen Fuchs in Environmental Stressors in Health and Disease, 2001
Atmospheric pollutants, largely arising as primary and secondary products of combustion, represent an important source of oxidative and nitrosative stress to Earth’s biosystem. Since the various biosurfaces are directly exposed to these pollutant stresses, it is not surprising that living organisms have developed complex integrated extracellular and intracellular defense systems against stresses related to atmospheric reactive oxygen species (ROS) and reactive nitrogen species (RNS), including ozone (O3) and nitrogen dioxide (NO2). Animal epithelial surfaces, including the delicate respiratory tract surfaces, contain an antioxidant network that would be expected to provide defense against environmental stress caused by ambient ROS and RNS, thus ameliorating their injurious effects on underlying cellular constituents.
Oxidative Stress and Inflammation
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
This chapter describes the oxidative stress and different inflammatory diseases with special reference to neurological disorders. Neuroinflammation mediates neurodegeneration by inducing the release of excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby causing oxidative stress and further inflammation. The NLRP3 inflammasome signaling pathway activation-mediated by oxidative stress in microglia is crucial for the development and progression of various neurodegenerative diseases. However, during oxidative stress, neuroinflammation, or mitochondrial dysfunction, the antioxidant response might be insufficient to ameliorate the redox imbalance. Oxidative stress is considered to be an important process that contributes to the progression of Huntington’s disease (HD) as it has been well documented in HD patients. Metabolic reactions generate ROS in different cellular compartments. Although mitochondria are regarded as the primary site and the electron transport chain as the main source of ROS, there are other sources which are also responsible for the generation of a significant amount of ROS, thereby resulting in different pathological conditions.
Production of nitric oxide-derived reactive nitrogen species in human oral cavity and their scavenging by salivary redox components
Published in Free Radical Research, 2005
Umeo Takahama, Sachiko Hirota, Takayuki Oniki
Nitrite is reduced to nitric oxide (NO) in the oral cavity. The NO generated can react with molecular oxygen producing reactive nitrogen species. In this study, reduction of nitrite to NO was observed in bacterial fractions of saliva and whole saliva. Formation of reactive nitrogen species from NO was detected by measuring the transformation of 4,5-diaminofluorescein (DAF-2) to triazolfluorescein (DAF-2T). The transformation was fast in bacterial fractions but slow in whole saliva. Salivary components such as ascorbate, glutathione, uric acid and thiocyanate inhibited the transformation of DAF-2 to DAF-2T in bacterial fractions without affecting nitrite-dependent NO production. The inhibition was deduced to be due to scavenging of reactive nitrogen species, which were formed from NO, by the above reagents. The transformation of DAF-2 to DAF-2T was faster in bacterial fractions and whole saliva which were prepared 1–4 h after tooth brushing than those prepared immediately after toothbrushing. Increase in the rate as a function of time after toothbrushing seemed to be due to the increase in population of bacteria which could reduce nitrite to NO. The results obtained in this study suggest that reactive nitrogen species derived from NO are continuously formed in the oral cavity and that the reactive nitrogen species are effectively scavenged by salivary redox components in saliva but the scavenging is not complete.
The mechanisms for nitration and nitrotyrosine formation
Published in Free Radical Research, 2001
Ceri Oldreive, Catherine Rice-Evans
The detection of 3-nitro-L-tyrosine residues associated with many disease states, including gastric cancer, has implicated a role for peroxynitrite in vivo, and thus endogenously produced nitric oxide and superoxide. Additionally, dietary nitrate has been suggested to be involved in the pathogenesis of gastric cancer through a mechanism involving reduction to nitrite and subsequent formation of potentially mutagenic nitrosocompounds. Studies have now demonstrated that a multitude of reactive nitrogen species other than peroxynitrite are capable of producing nitrotyrosine. Thus, we have reviewed the evidence that dietary nitrate, amongst other reactive nitrogen species, may contribute to the body burden of nitrotyrosine.
Effect of procyanidins from
Published in Redox Report, 1999
G. Rimbach, F. Virgili, Y.C. Park, L. Packer
The effects of reactive nitrogen species on glutathione homeostasis in human endothelial ECV 304 cells challenged by 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) or RAW 264.7 activated macrophages using a co-culture model were investigated. SIN-1 or macrophages activated by lipopolysaccharide plus interferon-gamma induced a significant glutathione decrease in ECV 304 cells. Pre-incubation of ECV 304 cells with French maritime pine bark extract containing mainly oligomeric procyanidins protected endothelial cells from activated macrophage-induced glutathione depletion. Data demonstrate that reactive nitrogen species generated with different kinetics and mechanisms impair glutathione levels in endothelial cells, and that pine bark extract significantly enhances antioxidant defenses.