The Molecular Mechanism Of Action Of Antioxidants

Antioxidants have neuroprotective, antioxidant anti-apoptotic activity at low concentrations, whereas at high concentrations they induce pro-oxidant and neurotoxic pro-apoptotic actions in cell cultures and in vivo models of neurodegenerative diseases. Our recent studies (10,28) provide new insights into the molecular events involved in the dose-dependent anti- and or pro-apoptotic activities of catechol-derived and indoleamine compounds at low and high concentrations. For this purpose, low...

Glutathione and Immune Function

One of the first indications that glutathione influences aspects of immune function, which are related to T lymphocytes, came from a study in which the GSH content of these cells was measured in a group of healthy volunteers (65). The numbers of helper (CD4+) and cytotoxic (CD8+) T cells increased in parallel with intracellular GSH concentrations up to 30 nmol mg of protein. However, the relationship between cellular glutathione concentrations and cell numbers was complex, with numbers of both...

Effects of Folic Acid on Immune Function

Folic acid plays a crucial role in DNA synthesis suggesting that every aspect involving cell proliferation might be affected by deficiency in the vitamin. Indeed, cell-mediated immunity is especially affected by deficiency in humans and animals (83). Folate deficiency also impairs natural killer cell activity in rats (84). As the vitamin is also intimately involved in sulfur amino acid metabolism, it might be expected that the vitamin would modulate anti-oxidant status and immune function....

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Figure 6.1 The effect of DA, R-APO, EGCG, and melatonin on cellular viability. NB SH-SY5Y cells were pretreated with increasing concentrations of DA, R-APO, EGCG, and melatonin for 24 h. Cell viability was assessed by MTT test, and expressed as a percent of untreated control without the compounds. The results are expressed as the mean + SD. The experiments were repeated at least three times in duplicates. diseases and their models. The combined implementation of these methods may shed light on...

Effects of Vitamin B6 on Immune Function

Vitamin B6, although having no anti-oxidant properties, plays an important part in anti-oxidant defenses because of its action in the metabolic pathway for the formation of cysteine, which, as indicated earlier, is the rate limiting precursor in glutathione synthesis. Vitamin B6 status has widespread effects on immune function (79). Vitamin B6 deficiency causes thymic atrophy and lymphocyte depletion in lymph nodes and spleen. Antigen processing is unaffected. However, the ability to make...

Decline In Antioxidant Defenses And Increased Oxidant Damage Follows Infection And Injury

There is a growing body of evidence that anti-oxidants suppress inflammatory components of the response to infection and trauma and enhance components related to cell-mediated immunity. The reverse situation applies when anti-oxidant defenses become depleted. Although the body strives to maintain them, observations in experimental animals and patients indicate that anti-oxidant defenses become depleted during infection and after injury. For example, in mice infected with influenza virus, there...

Effects of Precursors of GSH on Immune Function

A number of strategies have evolved to raise GSH concentrations in depleted individuals. As shown in Fig. 5.4, there are three potential ways of enhancing cellular GSH content administration of the three amino acids (cysteine, glutamic acid, and glycine) that comprise the tri-peptide, either singly or in various combinations administration of cofactors for the metabolic pathways leading to GSH production, that is, vitamin B6, riboflavin, and folic acid administration of synthetic compounds,...

Taurine and Immune Function

Taurine, together with sulfate, can be regarded as biochemical end products of cysteine metabolism. However, it is apparent that taurine also plays a role in immune function. It is the most abundant free nitrogenous compound (often incorrectly classified as an amino acid) in cells. It is a membrane stabilizer and regulates calcium flux thereby controlling cell stability. It has been shown to possess anti-oxidant properties and to regulate the release of pro-inflammatory cytokines in hamsters,...

References

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Mechanisms Underlying Low Grade Inflammation During Aging

There are a number of potential mechanisms for the higher level of chronic inflammation and hence oxidant stress, observed in the elderly than in younger subjects. The first of these is that the elderly are experiencing a higher level of asymptomatic bacteriuria. This possibility was studied in 40 consecutive patients (age 70-91 years) admitted to hospital for functional disability. Patients were examined for the presence or absence of bacteria in urine. Twenty subjects had positive urine...

Lifespan Regulation In Drosophila

The mutations of Drosophila melanogaster in the chico gene that encodes an insulin receptor substrate in insulin IGF-I signaling extend lifespan by up to 48 (24). The chico mutations increase resistance to starvation stress but not to heat stress. Slight resistance to oxidative stress (paraquat) is seen in chico heterozygotes chi + but not in homozygotes chi chi . The effects on stress resistance of chico mutations are not so marked as in the daf-2 and age-1 mutations of C. elegans. Total SOD...

Mechanisms Of The Effects Of Oxidants And Antioxidants On Inflammation And Immune Function

The oxidant molecules produced by the immune system to kill invading organisms may activate at least two important families of proteins that are sensitive to changes in cellular redox state. The families are nuclear transcription factor kappa B (NFkB) and activator protein 1 (API). These transcription factors act as control switches for biological processes, not all of which, as illustrated earlier, are of advantage to the individual. NFkB is present in the cytosol in an inactive form, by...

Fatty Acids Gene Expression and Coronary Heart Disease CHD

Fatty Acid Structure and Tissue Sources 182 Fatty Acid Regulation of Gene Expression 187 PUFA and Hepatic Lipogenesis 187 PUFA Induction of Lipid Oxidation 189 Fatty Acids and Adipocytes Gene Expression 189 Fatty Acid and Arterial Wall Gene Expression 190 PUFA and Their Cellular Mechanisms of Action 191 Peroxisome Proliferator-Activated Receptors (PPAR) 192 PPAR Ligands 193 Other Families of Transcription Factors that Mediate the PUFA PUFA Derivative Effect on Gene Expression 193 Sterol...

Oxidants Antioxidants And NfkB Mediated Gene Expression In The Endothelium

H2o2 Endothelial Cells

The biology of NF-kB in endothelial cells, and its possible modification by dietary components, has attracted considerable attention because of accumulating evidence that this transcription factor might play a major role in atherogenesis. First, activated NF-kB is present in the atheromatous plaque in SMC and macrophages as well as endothelial cells but is absent in cells of the healthy arterial wall (8). Second, NF-kB is activated by an array of stimuli thought to play a key role in the...

Reproductive System and Lifespan

The somatic gonad and germ line can be selectively deleted by laser beam irradiation of their precursor cells at the early larval stage in C. elegans. Hsin et al. (77) ablated the germ line and left the somatic gonad intact resulting in a large extension of lifespan in wild-type animals. Ablation of the somatic gonad (entire gonad organ) has no effect on wild-type lifespan. In the case of certain daf-2 mutants, ablation of the somatic gonad as well as the germ line promote an extended lifespan....

GSTM1 Biomarkers

The effects of diet on activity of the GST enzymes have been demonstrated in several studies. For example, in a feeding study with healthy volunteers, activity of GSTA and GST serum levels were measured in GSTM1(+) and GSTM1(- -) subjects. Brassica vegetable diets increased GSTA by 26 and GST serum activity by 7 in the GSTMl-null individuals, particularly in women. Among the GSTM1(+) women, GSTM activity was increased by both brassica (18 ) and the allium (26 ) diets (42). Palli et al. (43)...

Series Introduction

Through evolution, oxygen itself a free radical was chosen as the terminal electron acceptor for respiration. The two unpaired electrons of oxygen spin in the same direction thus, oxygen is a biradical. Other oxygen-derived free radicals, such as superoxide anion or hydroxyl radicals, formed during metabolism or by ionizing radiation are stronger oxidants, i.e., endowed with a higher chemical reactivity. Oxygen-derived free radicals are generated during oxidative...