scholarly journals N-Acetyl-Cysteine supplementation lowers high homocysteine plasma levels and increases Glutathione synthesis in the trans-sulfuration pathway

2019 ◽  
Vol 13 (4) ◽  
pp. 234-240
Author(s):  
Federico Cacciapuoti
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Active Form ◽  
The Body ◽  
Glutamate Cysteine Ligase ◽  
Pathological Conditions ◽  
Transsulfuration Pathway ◽  
Antioxidant Function ◽  
Acetyl Cysteine ◽  
Rate Limiting

Glutathione (GSH), a compound derived of a combination of three amino acids – cysteine, glycine and glutamine – is the final product of homocysteine (Hcy) metabolism  in the transsulfuration pathway. The major determinants of GSH synthesis are the availability of cysteine and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). A deficiency in  transsulfuration pathway leads to excessive Hcy production (HHcy) and reduced GSH synthesis. This tripeptide, that exists in the reduced or active  form (GSH) and oxidized variant (GSH), is the main antioxidant of the  body.  Independently of its antioxidant function, the compound  has an anti-inflammatory role too, reducing the production of interleukines and the expression of TNF-alfa and iNOS synthase. A dysregulation of GSH synthesis is recognized as contributing factor to the pathogenesis of many pathological conditions. But, the insufficiency of the transsulfuration pathway is also responsible of HHcy. Besides, this condition  decreases the activity of cellular “gluthatione peroxidase”, an intracellular antioxidant enzyme that reduces hydrogen peroxide to water with the prevalence of GSSH on GSH. The consequent GSH/GSSH impaired ratio also causes some common cardiovascular and neurodegenerative disorders. In both occurrences, N-Acetyl-Cysteine (NAC) supplementation supplies the cysteine necessary for GSH synthesis and contemporarily reduces HHcy, improving  the GPx1 activity and further reducing oxidative stress.

Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders

2020 ◽  
Vol 20 (13) ◽  
pp. 1142-1153 ◽  
Author(s):  
Sreyashi Chandra ◽  
Md. Tanjim Alam ◽  
Jhilik Dey ◽  
Baby C. Pulikkaparambil Sasidharan ◽  
Upasana Ray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
The Body ◽  
Therapeutic Approaches ◽  
Cns Disorders ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Present Understanding ◽  
Lateral Sclerosis

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

scholarly journals POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

2021 ◽  
pp. 125-136
Author(s):  
S. A. Tsiumpala ◽  
K. M. Starchevska ◽  
V. I. Lushchak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Old Age ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
The Body ◽  
Biologically Active ◽  
Inflammatory Processes ◽  
The Brain ◽  
Potential Use

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

scholarly journals Methionine Nutrition and Metabolism: Insights from Animal Studies to Inform Human Nutrition

2020 ◽  
Vol 150 (Supplement_1) ◽  
pp. 2518S-2523S ◽  
Author(s):  
Rajavel Elango
Keyword(s):  
Animal Studies ◽  
Animal Feed ◽  
Lessons Learned ◽  
The Body ◽  
Methyl Donors ◽  
Transsulfuration Pathway ◽  
Indispensable Amino Acids ◽  
Rate Limiting ◽  
Plant Sources

ABSTRACT Methionine is a nutritionally indispensable amino acid, and is unique among indispensable amino acids due to its sulfur atom. Methionine is involved in cysteine synthesis via the transsulfuration pathway, which is rate limiting for the key antioxidant molecule, glutathione. Methionine is also the primary methyl donor in the body through S-adenosylmethionine via the transmethylation pathway, which is involved in the synthesis of several key metabolites including creatine and phosphatidylcholine. Methionine can also be remethylated from homocysteine, in the presence of betaine via choline and/or folate. Thus methionine demands from a dietary perspective are regulated not only by the presence of cysteine in the body, but also by the demands in vivo for the various metabolites formed from it, and also by the presence of these compounds in foods. Indeed, methionine, cysteine, and the various methyl donors/acceptors vary in human foods, and thus regulate methionine availability, especially under conditions of growth and development. Much of our understanding of methionine nutrition and metabolism arises from experiments in animal models. This is because most animal feed formulations are plant-based and plant sources are relatively low in methionine and cysteine amounts. Thus, this brief review will touch on some broad aspects of human methionine nutrition, including requirements in different life stages, disease, and bioavailability, with some examples from the insights/lessons learned from experiments initially conducted in animals.

scholarly journals Oxidative Stress Mediates UVC-Induced Increases in Epidermal Autofluorescence of C57 Mouse Ears

2018 ◽  
Author(s):  
Mingchao Zhang ◽  
Dhruba Tara Maharjan ◽  
Yujia Li ◽  
Weihai Ying
Keyword(s):  
Oxidative Stress ◽  
Significant Role ◽  
Cysteine Protease ◽  
The Body ◽  
Skin Damage ◽  
Multiple Regions ◽  
Acetyl Cysteine ◽  
Keratin 1

AbstractOur recent study has reported that UV-induced epidermal autofluorescence (AF) can be used as a novel biomarker for predicting UV-induced skin damage, which is originated from UV-induced, cysteine protease-mediated keratin 1 degradation. A key question regarding these findings is: Does oxidative stress play a significant role in the UV-induced epidermal AF and keratin 1 proteolysis? In our current study, we administered the widely used antioxidant N-acetyl cysteine (NAC) into the skin of mouse ears to test our hypothesis that oxidative stress mediates UV-induced increases in the epidermal AF and keratin 1 degradation. Our study has shown that NAC administration can significantly attenuate the UVC-induced AF increases. The NAC administration can also significantly decrease the UVC-induced keratin 1 degradation. Collectively, our findings have indicated that the oxidative stress induced by UVC is causative to the UVC-induced increases in epidermal AF and keratin 1 proteolysis. Moreover, since oxidative stress is significantly increased in multiple regions of the body in several major diseases, the oxidative stress-induced increases in epidermal AF may become a novel biomarker for diagnosis of major diseases.

scholarly journals Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

2021 ◽  
Vol 22 (2) ◽  
pp. 630
Author(s):  
Ewa Maria Kratz ◽  
Katarzyna Sołkiewicz ◽  
Adriana Kubis-Kubiak ◽  
Agnieszka Piwowar
Keyword(s):  
Oxidative Stress ◽  
Histone Deacetylases ◽  
Wide Spectrum ◽  
Cellular Level ◽  
The Body ◽  
Human Organism ◽  
Biochemical Processes ◽  
Pathological Conditions ◽  
Available Information

Sirtuins (SIRTs), enzymes from the family of NAD+-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.

Iron chelation as a potential therapy for neurodegenerative disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1304-1308 ◽  
Author(s):  
Robert C. Hider ◽  
Yongmin Ma ◽  
Francisco Molina-Holgado ◽  
Alessandra Gaeta ◽  
Sourav Roy
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Rational Design ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Therapeutic Agents ◽  
Disease States ◽  
Pathological Conditions ◽  
Pharmacological Targets ◽  
And Oxidative Stress

Neurodegenerative disorders include a variety of pathological conditions, which share similar critical metabolic processes such as protein aggregation and oxidative stress, both of which are associated with the involvement of metal ions. Chelation therapy could provide a valuable therapeutic approach to such disease states, since metals, particularly iron, are realistic pharmacological targets for the rational design of new therapeutic agents.

scholarly journals Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yue Shang ◽  
Yaw L. Siow ◽  
Cara K. Isaak ◽  
Karmin O
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Plasma Homocysteine ◽  
Glutathione Depletion ◽  
Glutamate Cysteine Ligase ◽  
Glutathione Biosynthesis ◽  
Transsulfuration Pathway ◽  
Distant Organ

Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction. Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury. The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance. In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver function. This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of cystathionineγ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway. These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion.

scholarly journals The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Michal Pokusa ◽  
Alžbeta Kráľová Trančíková
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Membrane Dynamics ◽  
The Body ◽  
Hypoxic Conditions ◽  
Oxidative Balance ◽  
Immune System Activation ◽  
Correct Function ◽  
Endocrine Secretion

Traditionally, oxidative stress as a biological aspect is defined as an imbalance between the free radical generation and antioxidant capacity of living systems. The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic conditions, and dysregulation of gene expression are all molecular pathogenic mechanisms closely associated with oxidative stress and underpin systemic changes in the body. These also include aspects such as chronic immune system activation, the impairment of cellular structure renewal, and alterations in the character of the endocrine secretion of diverse tissues. All of these mentioned features are crucial for the correct function of the various tissue types in the body. In the present review, we summarize current knowledge about the common roots of metabolic and neurodegenerative disorders induced by oxidative stress. We discuss these common roots with regard to the way that (1) the respective metal ions are involved in the maintenance of oxidative balance and (2) the metabolic and signaling disturbances of the most important biometals, such as Mg2+, Zn2+, Se2+, Fe2+, or Cu2+, can be considered as the central connection point between the pathogenesis of both types of disorders and oxidative stress.

Iron Metabolism in the Human Body and Setting its Hygienic Limits for Drinking Water. Review. Part 2

2020 ◽  
Vol 99 (5) ◽  
pp. 504-508
Author(s):  
Natalija A. Egorova ◽  
N. V. Kanatnikova
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Subcutaneous Tissue ◽  
Allergic Diseases ◽  
The Body ◽  
Urogenital System ◽  
High Iron Content ◽  
Labile Iron Pool

Iron is an assential element for the growth, division, differentiation and functioning of any cell in the body. Iron is virtually important for human and danger at the same time, because with excessive accumulation it causes oxidative stress with formation of highly active oxygen radicals and reactive form of nitrogen that can destroy cell membranes, proteins, nucleic acids, reduce cell viability, with, according to modern concepts, can contribute to the development of many diseases (cardiovascular, rheumatic, gastrointestinal, neurodegenerative, oncological, metabolic and others), and also accelerate the aging process. Part 1 of this review discussed the issues of iron metabolism in human, including its regulation at the cellular and systemic levels, the intake, transport, use, accumulation and export of iron in cells, the role of the labile iron pool in the cytoplasm of cells and plasma non-transferrin bound iron. Data are provided on the causes, frequency and significance of iron overload in the formation of free radicals and the development of oxidative stress. Part 2 of the review provides information on diseases associated with iron overload as well as information on ferroptosis - a new type of iron-dependent regulated cell death. Attention is paid to the works of domestic authors, where it was found that prolonged use of drinking water with a high iron content is unfavorable for the population and leads to an increase in the overall incidence, the development of the diseases of the blood, skin and subcutaneous tissue, musculoskeletal system, digestive system, urogenital system, and allergic diseases. Separate publications are cited on the possibility of a negative effect of iron at concentrations in water of 0.3 mg/l and lower. The material of the review emphasizes the preventive significance of caution attitude to regulating iron in the water in the Russian Federation, where 1/3 of the population uses iron-containing water for drinking, and substantiate the feasibility of establishing a hygienic limit for iron in water not higher than 0.3 mg/l.

Innovative approaches to the correction of chronotrope status of pregnant and lactating women

2016 ◽  
pp. 37-40
Author(s):  
S.I. Zhuk ◽  
◽  
K.K. Bondarenko ◽  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Active Form ◽  
Biologically Active ◽  
Lactating Women ◽  
Pathological Conditions ◽  
Prevention And Treatment ◽  
The Impact ◽  
High Bioavailability ◽  
Key Words Mthfr

Most recent studies show the impact of violations in the metabolism of folate and metin period in the pathogenesis of neural tube defects (NTD) of the fetus. Metafolin has a number of advantages, which primarily includes direct intake of substances in biologically active form and the optimum effect, even in the case when the patient homozygote and/or heterozygote genotype 677С T polymorphism in MTHFR. With the aim of prevention and treatment of various pathological conditions related to folate deficiency during pregnancy, it is advisable to apply vitamin-mineral complexes, containing metafolin - active form of folate with high bioavailability. Key words: MTHFR, metafolin, folic acid, pregnancy.

Sign in / Sign up

Export Citation Format

Share Document