Hydroxyl radicals cause oxidative damage to cells because they unspecifically attack biomolecules [22] located less than a few nanometres from its site of generation and are involved in cellular disorders such as neurodegeneration [23, 24], cardiovascular disease [25], and cancer [26, 27].
24More
Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde... - 0 views
-
It is generally assumed that in biological systems is formed through redox cycling by Fenton reaction, where free iron (Fe2+) reacts with hydrogen peroxide (H2O2) and the Haber-Weiss reaction that results in the production of Fe2+ when superoxide reacts with ferric iron (Fe3+)
- ...20 more annotations...
-
Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously
-
under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death
-
The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination
-
Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.
-
Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied
-
MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)
-
MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community
-
4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”
-
Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)
-
MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases
-
Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk
1More
Lipoic acid suppresses compound 48/80-induced anaphylaxis-like reaction - 0 views
1More
Macrophagic myofasciitis: characterization and pathophysiology - 0 views
15More
Ascorbic acid: Chemistry, biology and the treatment of cancer - 0 views
-
iron and ascorbate has long been used as an oxidizing system; the combination of these two reagents is referred to as the Udenfriend system
- ...11 more annotations...
-
pharmacokinetic data indicate that intravenous administration of ascorbate can bypass this tight control resulting in highly elevated plasma levels
-
ascorbate readily oxidizes to produce H2O2, pharmacological ascorbate has been proposed as a prodrug for the delivery of H2O2 to tumors
-
Ascorbate is an excellent reducing agent and readily undergoes two consecutive, one-electron oxidations to form ascorbate radical (Asc•−) and dehydroascorbic acid (DHA)
-
Ascorbate oxidizes readily. The rate of oxidation is dependent on pH and is accelerated by catalytic metals
-
In near-neutral buffers with contaminating metals, the oxidation and subsequent loss of ascorbate can be very rapid
-
Ascorbate is an excellent one-electron reducing agent that can reduce ferric (Fe3+) to ferrous (Fe2+) iron, while being oxidized to ascorbate radical
-
In a classic Fenton reaction, Fe2+ reacts with H2O2 to generate Fe3+ and the very oxidizing hydroxyl radical
-
e presence of ascorbate can allow the recycling of Fe3+ back to Fe2+, which in turn will catalyze the formation of highly reactive oxidants from H2O2
-
Depending on concentrations, the effects of ascorbate on models of lipid peroxidation can be pro- or antioxidant
4More
ingentaconnect Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Re... - 0 views
www.ingentaconnect.com/...art00009
ATMs obesity inflammation inflammatory reaction insulin resistance IR diabetes DM type II macrophages
shared by Nathan Goodyear on 10 Jan 12
- No Cached
1More
Elevated Troponin and Jarisch-Herxheimer Reaction in Tick-Borne Relapsing Fever: A Case... - 0 views
1More
Mechanisms of the pH- and Oxygen-Dependent Oxidation Activities of Artesunate - 0 views
1More
Role of iron in carcinogenesis: Cancer as a ferrotoxic disease - Toyokuni - 2009 - Canc... - 0 views
7More
Redox regulation in cancer - 0 views
-
Mitochondrial electron-transport chain and other oxidizing agents are the prime pathways that generate excess ROS in vivo
-
Permanent modification of genetic material resulting from the oxidative damage is one of the vital steps involved in mutagenesis that leads to carcinogenesi
-
The most frequent DNA mutations caused during oxidative stress, initiated by ionizing radiation and other environmental carcinogens are 7,8-dihydro-8-oxoguanine (8-Oxo-G) and Thymine Glycol (TG)
- ...3 more annotations...
38More
High-Dose Vitamin C for Cancer Therapy - PMC - 0 views
-
diabetes [8], atherosclerosis [9], the common cold [10], cataracts [11], glaucoma [12], macular degeneration [13], stroke [14], heart disease [15], COVID-19 [16], and cancer.
- ...35 more annotations...
-
Iron is found in the human body in the form of haemoglobin in red blood cells and growing erythroid cells.
-
iron is taken up by the majority of cells in the form of a transferrin (Tf)-Fe(III) complex that binds to the cell surface receptor transferrin receptor 1 (TfR1)
-
the endosomal six transmembrane epithelial antigen of the prostate 3 (STEAP3) reduces Fe(III) (ferric ion) to Fe(II) (ferrous ion), which is subsequently transferred across the endosomal membrane by divalent metal transporter 1 (DMT1)
-
DHA is quickly converted to Vit-C within the cell, by interacting with reduced glutathione (GSH) [45,46,47]. NADPH then recycles the oxidized glutathione (glutathione disulfide (GSSG)) and converts it back into GSH
-
Fe(II) catalyzes the formation of OH• and OH− during the interaction between H2O2 and O2•− (Haber–Weiss reaction)
-
Ascorbate can efficiently reduce free iron, thus recycling the cellular Fe(II)/Fe(III) to produce more OH• from H2O2 than can be generated during the Fenton reaction, which ultimately leads to lipid, protein, and DNA oxidation
-
Asc•− and H2O2 were generated in vivo upon i.v Vit-C administration of around 0.5 g/kg of body weight and that the generation was Vit-C-dose reliant
-
increase in the expression of various iron-intake pathways or the downregulation of iron exporter proteins and storage pathways
-
Advanced breast tumor patients had substantially greater Fe(II) levels in their blood than the control groups without the disease
-
Vit-C is supplied, it oxidizes to DHA, and then is readily transported by GLUT-1 in mutant cells of KRAS or BRAF competing with glucose [46]. DHA is quickly converted into ascorbate inside the cell by NADPH and GSH [46,107]. This decrease reduces the concentration of cytosolic antioxidants and raises the intracellular ROS amounts
-
ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+ (a critical co-factor of GAPDH); thus, further reducing the GAPDH associated with a multifaceted metabolic rewiring
-
high-dose Vit-C recruited metabolites and increased the enzymatic activity in the pentose phosphate pathway (PPP), blocked the tri-carboxylic acid (TCA) cycle, and increased oxygen uptake, disrupting the intracellular metabolic balance and resulting in irreversible cell death, due to an energy crisis
-
Due to its great volatility at neutral pH [76], bolus therapy with mega-dose DHA has only transitory effects on tumor cells, both in vitro and in vivo.
1More
Increased frequency of delayed type hypersensitivity to metals in patients with connect... - 0 views
www.ncbi.nlm.nih.gov/...25636536
mercury gold nickel lupus autoimmune disease autoimmune disease RA rheumatoid arthritis arthritis Sjogren's
shared by Nathan Goodyear on 26 Sep 16
- No Cached
14More
Glutathione Redox Regulates Airway Hyperresponsiveness and Airway Inflammation in Mice ... - 0 views
-
γ-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-γ.
- ...10 more annotations...
-
these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by γ-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.
-
Through the release of Th2 cytokines, such as IL-4, IL-5, and IL-13, orchestrate the recruitment and activation of the primary effector cells of the allergic response: the mast cells and the eosinophils
-
Glutathione is the most abundant nonprotein sulfhydryl compound in almost all cells. This tripeptide plays a significant role in many biological processes. It also constitutes the first line of the cellular defense mechanism against oxidative injury along with SOD, ascorbate, vitamin E, and catalase, and is the major intracellular redox buffer in ubiquitous cell types
-
We have shown that glutathione redox status, namely the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in murine antigen-presenting cells (APC) plays a central role in determining which of the reductive and oxidative APC predominate during immune status, and the balance between reductive and oxidative APC regulates Th1/Th2 balance through production of IL-12
-
we have also shown that exposure of human alveolar macrophages to the Th1 cytokine IFN-γ or the Th2 cytokine IL-4 either increases or decreases the GSH/GSSG ratio, respectively, which regulates Th1/Th2 balance through IL-12 production
-
the ability to generate a Th1 or Th2 type response has turned out to depend not only on T cells but also on the intracellular glutathione redox status of APC
-
Th1 cytokine IFN-γ and Th2 cytokine IL-4 increases and decreases the GSH/GSSG ratio, respectively, and that this ratio influences LPS-induced IL-12 production from alveolar macrophages
-
administration of γ-GCE elevates GSH level and GSH/GSSG ratio in the lung, and ameliorates AHR and eosinophilic airway inflammation by altering the Th1/Th2 balance and suppressing chemokine production and eosinophil migration in a mouse asthma model
1More
Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory... - 0 views
34More
Progesterone metabolites in breast cancer - 1 views
erc.endocrinology-journals.org/...717.full
progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase
shared by Nathan Goodyear on 20 Feb 12
- No Cached
-
P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
-
these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
-
only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
- ...30 more annotations...
-
P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
-
These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
-
Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
-
The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
-
the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
-
In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
-
The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
-
he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
-
The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
-
altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
-
In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
-
Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
-
The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
-
Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
-
Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
-
αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
-
The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
-
The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
-
separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
-
The studies thus provided the first demonstration of the existence of specific P metabolite receptors
-
the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
-
Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
-
In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
-
The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
-
current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
1More
Effect of chronic stress associated with unemployment on salivary cortisol: overall cor... - 0 views
www.psychosomaticmedicine.org/...460.abstract
stress saliva salivary cortisol test testing hormone hormones evaluation
shared by Nathan Goodyear on 28 Nov 11
- No Cached
1More
Plasma testosterone in the general population, can... [Ann Oncol. 2014] - PubMed - NCBI - 0 views
-
prospective study of almost 9,000 men and women followed for 30 + years. The study found that there was a significant increased risk of early death after diagnosis of cancer with higher levels of Testosterone. The risk was increased by up to 80%. The incidence of cancer was unchanged. The study looked at total Testosterone via serum. The study is limited due to its limited look at hormones. Full Testosterone metabolism needs to be evaluated--including conversion to estrogens. Inflammatory cytokines need to be assessed and men and women need to be assessed separately as their reactions to hormones are quite different.
1More
Ginsenoside Rg3 Alleviates Lipopolysaccharide-Induced Learning and Memory Impairments b... - 0 views
www.ncbi.nlm.nih.gov/...PMC3825202
RG3 inflammation brain memory learning ginsenoside panax ginseng panax ginseng TNF-alpha IL-1beta cox-2 cognition
shared by Nathan Goodyear on 10 Apr 14
- No Cached
1More