scholarly journals The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
W. A. García-Suástegui ◽  
L. A. Ramos-Chávez ◽  
M. Rubio-Osornio ◽  
M. Calvillo-Velasco ◽  
J. A. Atzin-Méndez ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Free Radical ◽  
Metabolic Pathways ◽  
The Body ◽  
Oxygen Species ◽  
Brain Disorders ◽  
Toxic Agents ◽  
Major Organ ◽  
The Brain

Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

scholarly journals Ferroptosis and Brain Injury

2018 ◽  
Vol 40 (5-6) ◽  
pp. 382-395 ◽  
Author(s):  
Leslie Magtanong ◽  
Scott J. Dixon
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Brain Injuries ◽  
Basic Problem ◽  
Oxygen Species ◽  
Brain Disorders ◽  
Small Molecule Screening ◽  
The Relationship ◽  
The Brain

Ferroptosis is a nonapoptotic form of cell death characterized by the iron-dependent accumulation of toxic lipid reactive oxygen species. Small-molecule screening and subsequent optimization have yielded potent and specific activators and inhibitors of this process. These compounds have been employed to dissect the lethal mechanism and implicate this process in pathological cell death events observed in many tissues, including the brain. Indeed, ferroptosis is emerging as an important mechanism of cell death during stroke, intracerebral hemorrhage, and other acute brain injuries, and may also play a role in certain degenerative brain disorders. Outstanding issues include the practical need to identify molecular markers of ferroptosis that can be used to detect and study this process in vivo, and the more basic problem of understanding the relationship between ferroptosis and other forms of cell death that can be triggered in the brain during injury.

scholarly journals Modulation of Obesity and Insulin Resistance by the Redox Enzyme and Adaptor Protein p66Shc

2019 ◽  
Vol 20 (4) ◽  
pp. 985 ◽  
Author(s):  
Stefano Ciciliot ◽  
Gian Fadini
Keyword(s):  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Metabolic Pathways ◽  
Adaptor Protein ◽  
Oxygen Species ◽  
Related Protein ◽  
Redox Enzyme ◽  
Obesity And Diabetes ◽  
Promising Therapeutic Target

Initially reported as a longevity-related protein, the 66 kDa isoform of the mammalian Shc1 locus has been implicated in several metabolic pathways, being able to act both as an adaptor protein and as a redox enzyme capable of generating reactive oxygen species (ROS) when it localizes to the mitochondrion. Ablation of p66Shc has been shown to be protective against obesity and the insurgence of insulin resistance, but not all the studies available in the literature agree on these points. This review will focus in particular on the role of p66Shc in the modulation of glucose homeostasis, obesity, body temperature, and respiration/energy expenditure. In view of the obesity and diabetes epidemic, p66Shc may represent a promising therapeutic target with enormous implications for human health.

scholarly journals The Role of Oxidative Stress and Antioxidant Balance in Pregnancy

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Elsayed Metwally ◽  
Dildar Hussain Kalhoro ◽  
Muhammad Saleem Kalhoro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Gestational Diabetes ◽  
Embryo Implantation ◽  
Fetal Loss ◽  
The Body ◽  
Oxygen Species ◽  
In Pregnancy

It has been widely known that oxidative stress disrupts the balance between reactive oxygen species (ROS) and the antioxidant system in the body. During pregnancy, the physiological generation of ROS is involved in a variety of developmental processes ranging from oocyte maturation to luteolysis and embryo implantation. While abnormal overproduction of ROS disrupts these processes resulting in reproductive failure. In addition, excessive oxidative stress impairs maternal and placental functions and eventually results in fetal loss, IUGR, and gestational diabetes mellitus. Although some oxidative stress is inevitable during pregnancy, a balancing act between oxidant and antioxidant production is necessary at different stages of the pregnancy. The review aims to highlight the importance of maintaining oxidative and antioxidant balance throughout pregnancy. Furthermore, we highlight the role of oxidative stress in pregnancy-related diseases.

Hydrogen peroxide inhibits IL-12 p40 induction in macrophages by inhibiting c-rel translocation to the nucleus through activation of calmodulin protein

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1513-1520 ◽  
Author(s):  
Nooruddin Khan ◽  
Sheikh Showkat Rahim ◽  
Chandra Sekhar Boddupalli ◽  
Sheikh Ghousunnissa ◽  
Samavedan Padma ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Immune Response ◽  
Antimicrobial Activity ◽  
The Body ◽  
Interleukin 12 ◽  
Oxygen Species ◽  
H2o2 Treatment ◽  
Ifn Γ

Although the antimicrobial activity of reactive oxygen species (ROSs) is well defined, the role of ROSs in regulating the immune response of the body is not well understood. We now provide evidence that hydrogen peroxide (H2O2), a major component of ROSs, inhibits interleukin-12 (IL-12) p40 and IL-12 p70 induction in murine macrophages and catalase pretreatment prevents H2O2-mediated down-regulation of IL-12. Endogenous accumulation of H2O2/ROSs in macrophages treated with alloxan resulted in IL-12 p40 inhibition. Although nuclear expression of both p50 and p65 NF-κB increased on H2O2 exposure, nuclear c-rel level was inhibited. Overexpression of c-rel restored IL-12 p40 on stimulation with lipopolysaccharide plus IFN-γ during H2O2 treatment. H2O2 did not inhibit c-rel induction in cytosol; however, it prevented the transport of c-rel from cytosol to the nucleus. H2O2 activated calmodulin (CaM) protein in the cytosol, which subsequently sequestered c-rel in the cytosol preventing its transport to the nucleus. The CaM inhibitor trifIuoperazine increased both nuclear c-rel and IL-12 p40 levels in H2O2-treated macrophages, emphasizing a role of CaM in these processes. H2O2/ROSs thus down-regulate IL-12 induction in macrophages by a novel pathway inhibiting c-rel translocation to the nucleus through activation of CaM protein.

Systems biology of antioxidants

2012 ◽  
Vol 123 (3) ◽  
pp. 173-192 ◽  
Author(s):  
Ramaroson Andriantsitohaina ◽  
Lucie Duluc ◽  
Julio C. García-Rodríguez ◽  
Lizette Gil-del Valle ◽  
Mariela Guevara-Garcia ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Free Radical ◽  
Systems Biology ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Free Radical Damage ◽  
Radical Damage ◽  
Ros Reactive Oxygen Species

Understanding the role of oxidative injury will allow for therapy with agents that scavenge ROS (reactive oxygen species) and antioxidants in the management of several diseases related to free radical damage. The majority of free radicals are generated by mitochondria as a consequence of the mitochondrial cycle, whereas free radical accumulation is limited by the action of a variety of antioxidant processes that reside in every cell. In the present review, we provide an overview of the mitochondrial generation of ROS and discuss the role of ROS in the regulation of endothelial and adipocyte function. Moreover, we also discuss recent findings on the role of ROS in sepsis, cerebral ataxia and stroke. These results provide avenues for the therapeutic potential of antioxidants in a variety of diseases.

scholarly journals The Roles of Monocyte and Monocyte-Derived Macrophages in Common Brain Disorders

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Mingxia Zhao ◽  
Houzhen Tuo ◽  
Shuhui Wang ◽  
Lin Zhao
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Current Knowledge ◽  
The Body ◽  
Disease Models ◽  
Brain Disorders ◽  
And Function ◽  
The Brain ◽  
Complex Organ

The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients’ normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer’s disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.

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