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Title
Tissue glutathione, nutrition, and oxidative stress.
Author
Bray TM; Taylor CG
Address
Department of Nutritional Sciences, University of Guelph, ON,
Canada.
Source
Can J Physiol Pharmacol, 71(9):746-51 1993 Sep
Abstract
glutathione, a cysteine-containing tripeptide, is the most abundant
nonprotein thiol in mammalian cells. glutathione plays an important
role in the detoxification of xenobiotic compounds and in the
antioxidation of reactive oxygen species and free radicals. Because
of its multiple functions in various tissues and its involvement
in many diseases and malnutrition, a clear understanding of the
interrelationships among tissue glutathione, nutrition, and oxidative
stress is clinically relevant. The focus of this review is to
discuss the regulation of tissue glutathione concentration by
diet and nutritional status, and to apply this information to
those diseases and malnutrition in which decreased tissue glutathione
and increased oxidative stress are implicated. A potential strategy
to rapidly restore glutathione for both antioxidant and immune
defense systems before therapeutic treatment in malnourished
patients is discussed.
Title
glutathione depletion in rats impairs T-cell and macrophage immune
function.
Author
Robinson MK; Rodrick ML; Jacobs DO; Rounds JD; Collins KH; Saporoschetz
IB; Mannick JA; Wilmore DW
Address
Laboratory for Surgical Metabolism, Brigham and Women's Hospital,
Harvard Medical School, Boston, Mass. 02115.
Source
Arch Surg, 128(1):29-34; discussion 34-5 1993 Jan
Abstract
Critical illness is associated with both immunosuppression and
glutathione deficiency. We determined if in vivo depletion of
glutathione would adversely affect immune status. Rats with normal
glutathione levels and those with glutathione stores depleted
by diethyl maleate underwent analysis of splenocyte function
and mesenteric lymph node lymphocyte function. Lymphocytes of
the spleen and mesenteric lymph nodes were tested for concanavalin
A proliferative response and interleukin 2 production. Tumor
necrosis factor and interleukin 6 secretion by splenic adherent
cells was also measured. glutathione-depleted animals had significantly
decreased lymphocyte proliferation and decreased production of
tumor necrosis factor and interleukin 6 but unaltered interleukin
2 production. These findings indicate that in vivo glutathione
deficiency impairs macrophage and T-cell function. Because glutathione
depletion may occur in sepsis, trauma, and shock, treatments
that help maintain glutathione levels may enhance immunocompetence
and thus improve the ability of patients to recover from critical
illness.
Title
Imbalance between oxidants and antioxidants in the lungs of HIV-seropositive
individuals.
Author
Buhl R
Address
Pulmonary Department/ZIM, Frankfurt University Hospital, Germany.
Source
Chem Biol Interact, 91(2-3):147-58 1994 Jun
Abstract
Following the initial infection with HIV, there is evidence of
immune dysfunction despite an apparent normal clinical state.
In the context that the lung is a major site affected by opportunistic
infection, and that some components of the immune system are
activated during early HIV infection, we hypothesized that there
may be activation of alveolar macrophages (AM), a key component
of the pulmonary host defense system. Compared to cells from
normal individuals, AM of asymptomatic HIV-seropositive (HIV+)
individuals (CDC-stage II) spontaneously released significantly
more superoxide anion (O2-.) (P < 0.002). The O2-. release
by AM of HIV-infected individuals was comparable to the spontaneous
O2-.-release by AM of cigarette smokers (P > 0.6), a condition
often associated with chronic damage of respiratory tissues.
The destructive effects of oxidants are normally suppressed by
antioxidant defense systems. Evaluation of the concentrations
of glutathione, a major component of the pulmonary antioxidant
protective screen, demonstrated that the HIV+ state is also characterized
by a significant glutathione deficiency in lung epithelial lining
fluid (P < 0.001) and in venous plasma (P < 0.001). This
suggests that the alveolar structures of HIV+ individuals are
continuously exposed to increased amounts of toxic oxygen radicals
without adequate protection, i.e. the reactive oxygen metabolites
may cause sufficient tissue damage culminating in interstitial
lung disease. Further, since many immune functions are susceptible
to injury by extracellular oxidants, the consequences of an unsuppressed
oxidant burden in the lung may amplify the extent of local immunocompromise.
In addition, since glutathione plays an important role in modulating
lymphocyte activation and effector functions independent of its
antioxidant activity, the systemic glutathione deficiency may
contribute to the progressive global immune dysfunction that
characterizes HIV infection.
Title
Decreased levels of total and reduced glutathione in CD4+ lymphocytes
in common variable immunodeficiency are associated with activation
of the tumor necrosis factor system: possible immunopathogenic
role of oxidative stress.
Author
Aukrust P; Svardal AM; MÍuller F; Lunden B; Berge RK;
FrÍland SS
Address
Medical Department A, University of Oslo, National Hospital,
Norway.
Source
Blood, 86(4):1383-91 1995 Aug 15
Abstract
We have previously shown chronic immune activation and enhanced
generation of reactive oxygen species in common variable immunodeficiency
(CVI). In the present study, we examined levels of glutathione,
the dominant intracellular thiol, that play an important protective
role against oxidative and inflammatory stress in plasma and
in monocytes and lymphocyte subsets in 20 CVI patients and in
16 healthy controls. CD4+ lymphocytes from CVI patients had significantly
lower levels of both total and reduced glutathione as well as
a lower ratio of reduced to total glutathione compared with healthy
controls. This decrease in glutathione levels in CD4+ lymphocytes
was most pronounced in the CD45RA+ subset. Plasma levels of total
glutathione were also significantly decreased in CVI. In contrast,
monocytes from CVI patients exhibited increased levels of both
total and reduced glutathione compared with blood donor monocytes.
CVI patients had significantly raised serum levels of tumor necrosis
factor alpha (TNF alpha) and TNF alpha concentration was strongly
associated with glutathione depletion in CD4+ lymphocytes. Furthermore,
the lowest levels of both total and reduced glutathione were
found in a subgroup of CVI patients characterized by persistent
immune activation in vivo, decreased numbers of CD4+ lymphocytes
in peripheral blood, and splenomegaly. Finally, supplementation
of cell cultures with glutathione-monoethyl ester did significantly
enhance interleukin-2 production from peripheral blood mononuclear
cells in CVI patients. These glutathione abnormalities in CVI
indicate increased oxidative stress, particularly in CD4+ lymphocytes,
and intracellular depletion of reduced glutathione of the demonstrated
magnitude may have profound implications for CD4+ lymphocyte
function and the immunodeficiency in CVI.
Title
Antioxidants and immune response in aged persons: overview of
present evidence.
Author
Meydani SN; Wu D; Santos MS; Hayek MG
Address
Nutritional Immunology Laboratory, Jean Mayer US Department of
Agriculture Human Nutrition Research Center on Aging, Tufts University,
Boston, MA 02111, USA.
Source
Am J Clin Nutr, 62(6 Suppl):1462S-1476S 1995 Dec
Abstract
The oxidant-antioxidant balance is an important determinant of
immune cell function, including maintaining the integrity and
functionality of membrane lipids, cellular proteins, and nucleic
acids and controlling signal transduction and gene expression
in immune cells. Optimal amounts of antioxidants are needed for
maintenance of the immune response across all age groups. This
need might be more critical, however, in aged persons. Age-associated
dysregulation of immune response, particularly of T cell-mediated
function, is well documented. The well-known age-related increase
in free radical formation and lipid peroxidation contributes,
at least in part, to this phenomenon. We summarize animal and
human studies undertaken by ourselves as well as other investigators
on the effects of antioxidants, vitamin E, beta-carotene, and
glutathione on the immune response of aged persons. The underlying
mechanisms for the antioxidant nutrients' effects as well as
their health implications for aged persons are discussed.
Title
Prostaglandin E2 suppresses phytohemagglutinin-induced immune
responses of normal human mononuclear cells by decreasing intracellular
glutathione generation, but not due to increased DNA strand breaks
or apoptosis.
Author
Yu CL; Liu CL; Tsai CY; Sun KH; Liao TS; Lin WM; Chen HL; Yu
HS
Address
Department of Medicine, Veterans General Hospital-Taipei, Taiwan,
Republic of China.
Source
Agents Actions, 40(3-4):191-9 1993 Nov
Abstract
Prostaglandin E2 (PGE2) at concentrations more than 1 x 10(-8)
M markedly suppressed the cell proliferation and release of soluble
molecules of interleukin-2 receptor (sIL-2R), CD4 (sCD4) and
CD8 (sCD8) from phytohemagglutinin (PHA)-stimulated normal human
mononuclear cells (MNC) in a dose-related manner. To further
elucidate the subcellular mechanism of the inhibitory effect
of PGE2 on PHA-stimulated MNC, intracellular concentration of
glutathione (GSH) in PHA-stimulated MNC was sequentially measured
from day 1 to day 3 by enzymic method. Furthermore, the effect
of PGE2 on nuclear DNA including DNA strand breaks in alkali
treatment and DNA fragmentation (apoptosis) of PHA-stimulated
MNC were also measured. We found intracellular GSH levels were
significantly decreased in the early stage of lymphocyte activation
(day 1), but no evidence of increased DNA strand breaks or apoptotic
process appeared in 3-day culture. In addition, butathione sulfoximine
(a specific GSH inhibitor) and dibutyryl cyclic AMP also exhibited
both proliferation inhibition and GSH-decreasing effects on PHA-stimulated
MNC as well as PGE2. These results suggest that the immunosuppressive
effect of PGE2 is mediated by the decreased generation of intracellular
GSH, but not by the increased DNA strand breaks or apoptotic
mechanism in the cells.
Title
The biological activity of undenatured dietary whey proteins:
role of glutathione.
Author
Bounous G; Gold P
Address
Department of Surgery, Montreal General Hospital Research Institute,
Quebec.
Source
Clin Invest Med, 14(4):296-309 1991 Aug
Abstract
This study compared the effects of different sources of whey
protein concentrate (20 g/100 g diet) and of casein on the spleen,
liver, and heart glutathione content of C3H/HeJ mice, and on
the immune response of their spleen cells to sheep red blood
cells. Body weight curves were similar in all dietary groups.
Our data indicate that the humoral immune response is highest
in mice fed a dietary whey protein concentrate exhibiting the
highest solubility (undenatured conformation) and a greater relative
concentration of the thermolabile bovine serum albumin and immunoglobulins.
In addition, the mice fed this type of whey protein concentrate
exhibit higher levels of tissue glutathione. The presence in
the serum albumin fraction of glutamylcysteine groups (rare in
food protein) and the specific intramolecular bond as related
to the undenatured conformation of the molecule are considered
to be key factors in the glutathione-promoting activity of the
protein mixture.
Title
Effect of glutathione depletion and oral N-acetyl-cysteine treatment
on CD4+ and CD8+ cells.
Author
Kinscherf R; Fischbach T; Mihm S; Roth S; Hohenhaus-Sievert E;
Weiss C; Edler L; BÍartsch P; DrÍoge W
Address
Department of Immunochemistry, Deutsches Krebsforschungszentrum,
Heidelberg, Germany.
Source
FASEB J, 8(6):448-51 1994 Apr 1
Abstract
HIV-infected individuals and SIV-infected rhesus macaques have,
on the average, decreased plasma cysteine and cystine concentrations
and decreased intracellular glutathione levels. We show that
the cysteine supply and the intracellular glutathione levels
have a strong influence on the T cell system. A study of healthy
human subjects revealed that persons with intracellular glutathione
levels of 20-30 nmol/mg protein had significantly higher numbers
of CD4+ T cells than persons with either lower or higher glutathione
levels. Persons who moved during a 4-week observation period
from the optimal to the suboptimal range (10-20 nmol/mg) experienced,
on the average, a 30% decrease in CD4+ T cell numbers. This decrease
was prevented by treatment with N-acetyl-cysteine (GSH). GSH
caused this relative increase of CD4+ T cell numbers in spite
of decreasing glutathione levels and not by increasing the glutathione
level. Our studies suggest that the immune system may be exquisitely
sensitive not only against a cysteine and glutathione deficiency
but also against an excess of cysteine.
Title
Micronutrient profiles in HIV-1-infected heterosexual adults.
Author
Skurnick JH; Bogden JD; Baker H; Kemp FW; Sheffet A; Quattrone
G; Louria DB
Address
Department of Preventive Medicine and Community Health, UMDNJ-New
Jersey Medical School, Newark, New Jersey 07103-2714, USA.
Source
J Acquir Immune Defic Syndr Hum Retrovirol, 12(1):75-83 1996
May 1
Abstract
There is compelling evidence that micronutrients can profoundly
affect immunity. We surveyed vitamin supplement use and circulating
concentrations of 22 nutrients and glutathione in 64 HIV-1 seropositive
men and women and 33 seronegative controls participating in a
study of heterosexual HIV-1 transmission. We assayed antioxidants
(vitamins A, C, and E; total carotenes), vitamins B6 and B12,
folate, thiamin, niacin, biotin, riboflavin, pantothenic acid,
free and total choline and carnitine, biopterin, inositol, copper,
zinc, selenium, and magnesium. HIV-infected patients had lower
mean circulating concentrations of magnesium (p < 0.0001),
total carotenes (p = 0.009), total choline (p = 0.002), and glutathione
(p = 0.045), and higher concentrations of niacin (p < 0.0001)
than controls. Fifty-nine percent of HIV+ patients had low concentrations
of magnesium, compared with 9% of controls (p < 0.0001). These
abnormal concentrations were unrelated to stage of disease. Participants
who took vitamin supplements had consistently fewer low concentrations
of antioxidants, across HIV infection status and disease stage
strata (p = 0.0006). Nevertheless, 29% of the HIV+ patients taking
supplemental vitamins had subnormal levels of one or more antioxidants.
The frequent occurrence of abnormal micronutrient nutriture,
as found in these HIV+ subjects, may contribute to disease pathogenesis.
The low magnesium concentrations may be particularly relevant
to HIV-related symptoms of fatigue, lethargy, and impaired mentation.
Title
Antioxidants in nutrition and their importance in the anti-/oxidative
balance in the immune system
Author
Biesalski HK; Frank J
Address
Institut für Biologische Chemie und Ernährungswissenschaft,
Universität Hohenheim.
Source
Immun Infekt, 23(5):166-73 1995 Oct
Abstract
Free radicals and reactive oxygen species can damage cells and
tissues of biological organisms. Due to the fact that these compounds
are generated continuously in living cells defense mechanisms
must exist. This so-called antioxidative system ensures that
the formation of free radicals during different physiological
processes does not result in cellular damage. Free radicals (oxidants)
are produced form the immune system. The purpose of this immune
cell products is to destroy invading organisms and damaged tissue.
Oxidants enhance IL-1, IL-8 and TNF production in response to
inflammatory stimuli. Sophisticated antioxidant defense systems
like enzymes or vitamins protect directly and indirectly the
host against the damaging influence of oxidants. While endogenous
systems can hardly be influenced, exogenous antioxidants, delivered
by the diet, can be upregulated in the body. By this way the
pro-/antioxidative capacity can be balanced or even unbalanced.
Title
glutathione increases interleukin-2 production in human lymphocytes.
Author
Chen G; Wang SH; Converse CA
Address
University of Glasgow, Department of Medicine, Royal Infirmary,
U.K.
Source
Int J Immunopharmacol, 16(9):755-60 1994 Sep
Abstract
It is known that glutathione (GSH) has an immunological effect
on several features of the immune system. The present study investigated
the effects of GSH on interleukin-2 (IL-2) production from normal
human peripheral blood lymphocytes (PBL). The results showed
that both exogenous GSH and 2-mercaptoethanol (2-ME) significantly
increased intracellular GSH levels after PBL were incubated with
both agents. IL-2 production from PBL was markedly increased
at the presence of exogenous GSH (0.5-8 mmol/l) or 2-ME (12.5-50
mumol/l) which corresponded to 1.57-2.82 nmol/10(6) cells and
1.41 - 1.80 nmol/10(6) cells of intracellular concentrations
of GSH, respectively. However, IL-2 production seemed to reach
a steady level when exogenous GSH concentrations in cell culture
were between 2 and 8 mmol/l. The findings also showed that there
was a positive correlation between the IL-2 concentrations and
intracellular GSH levels. This study indicated that both exogenous
GSH and 2-ME were able to elevate intracellular GSH levels and
the increased intracellular GSH could increase IL-2 production
in vitro. It is suggested that GSH may exert its effects on the
immune system via the regulation of IL-2 synthesis. |
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