Sorry, this was for you Ashauna, GHS= Glutathione

[Guest guest]

Ashauna,

I sent this and did not put you name on it, sorry.

> Here is a little night reading, very informative, copied from

> Sharktank

> Enjoy,

>

> mom of a 10 wcf, Venanzio 7 nocf, Pepe 3 nocf

>

>

> Authors Roum JH. Borok Z. McElvaney NG. Grimes GJ. Bokser AD. Buhl

R.

> Crystal RG.

> Title Glutathione aerosol suppresses lung epithelial surface

> inflammatory cell-derived oxidants in cystic fibrosis

> Source Journal of Applied Physiology. 87(1):438-443, 1999 Jul.

>

> Abstract Cystic fibrosis (CF)

> is characterized by accumulation of activated neutrophils and

> macrophages on

> the respiratory epithelial surface (RES); these cells release toxic

> oxidants, which contribute to the marked epithelial derangements

seen

> in CF.

> These deleterious consequences are magnified, since reduced

> glutathione

> (GSH), an antioxidant present in high concentrations in normal

> respiratory

> epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate

the

> feasibility of increasing ELF GSH levels and enhancing RES

antioxidant

> protection, GSH aerosol was delivered (600 mg twice daily for 3

days)

> to

> seven patients with CF. ELF total, reduced, and oxidized GSH

> increased (P <

> 0.05, all compared with before GSH therapy), suggesting adequate RES

> delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-

> stimulated

> superoxide anion (O-2(-).) release by ELF inflammatory cells

> decreased after

> GSH therapy (P < 0.002). This paralleled observations that GSH

added

> in

> vitro to CF ELF inflammatory cells suppressed O-2(-). release (P <

> 0.001).

> No adverse effects were noted during treatment. Together, these

> observations

> demonstrate the feasibility of using GSH aerosol to restore RES

> oxidant-antioxidant balance in CF and support the rationale for

> further

> clinical evaluation. [References: 45] Publication Type Article

>

>

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Reznick AZ. Han D. Packer L.

> Title CIGARETTE SMOKE INDUCED OXIDATION OF HUMAN PLASMA PROTEINS,

> LIPIDS, AND ANTIOXIDANTS - SELECTIVE PROTECTION BY THE BIOTHIOLS

> DIHYDROLIPOIC ACID AND GLUTATHIONE

> Source Redox Report. 3(3):169-174, 1997 Jun.

>

> Abstract Exposure of human plasma to

> gas-phase cigarette smoke (CS) causes loss of human plasma

> antioxidants,

> protein modification (Frei et al, Biochem J. 1991 277: 133-138;

> Reznick et

> al, Biochem J. 1992 286: 607-611) and a minimal amount of lipid

> oxidation.

> Ascorbic acid was found to prevent CS-induced lipid peroxidation and

> glutathione (GSH) partially protected against protein modification,

as

> determined by loss of protein -SH groups and by increases in

carbonyl

> content as a measure of protein oxidation. In the present study we

> demonstrate that dihydrolipoic acid (0.25-1.0 mM) decreases CS-

induced

> protein carbonyls, alpha-tocopherol loss, and lipid hydroperoxide

> formation

> in plasma. In contrast GSH (1 mM) failed to influence CS-induced

loss

> of

> alpha-tocopherol, and was 50% as effective as dihydrolipoate in

> protecting

> against CS-induced protein carbonyl formation. On the other hand,

> lipoic

> acid (oxidized form of dihydrolipoic acid) and oxidized glutathione

> (GSSG)

> had minimal effect in protecting against the CS-induced protein

> modifications. These findings demonstrate that low molecular weight

> thiols

> are capable of modifying the effect of gas-phase CS on biological

> fluids.

> Dihydrolipoate appears to be particularly useful in that it was

shown

> to

> conserve ascorbic acid and a-tocopherol, i.e. supporting the

> antioxidant

> network concept in protection against protein and lipid oxidation.

> [References: 35] Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Marrades RM. Roca J. Barbera JA. Dejover L. Macnee W.

> roisin R.

> Title NEBULIZED GLUTATHIONE INDUCES BRONCHOCONSTRICTION IN PATIENTS

> WITH MILD ASTHMA

> Source American Journal of Respiratory & Critical Care Medicine. 156

> (2):425-430, 1997 Aug.

>

> Abstract To assess the effects on bronchial responsiveness of

> nebulized glutathione (GSH), one of

> the most efficient scavengers of oxidant substances in the airways,

we

> studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted

> [sD]) in

> a randomized, double-blind, cross-over, placebo-controlled fashion.

> Bronchial challenge was measured using both FEV1 and total pulmonary

> resistance (Rrs) by the forced oscillation technique. Patients

> received

> nebulized GSH (600 mg with 4 ml of 0.9% sodium chloride) or placebo

> (identical saline solution) over a period of 25 min, 1 wk apart.

> Placebo

> provoked subclinical mild bronchoconstriction (changes from

baseline:

> FEV1,

> -1%; Rrs, +17%); by contrast, GSH caused major airway narrowing

> (changes

> from baseline: FEV1, -19%; Rrs, +61%) and induced cough (four

> patients) or

> breathlessness (three patients). Differences between placebo and

GSH

> after

> challenge were also noticeable in both FEV1 (p = 0.03) and Rrs (p =

> 0.02).

> Neither osmolarity (660 mosm . kg(-1)) nor pH (3.0) of the GSH

> solution

> accounted for these effects. Nebulized salbutamol (5.0 mg) given

> before the

> GSH challenge blocked GSH-induced bronchoconstriction. Furthermore,

> GSH-induced FEV1 falls were inversely correlated with metabisulfite

> bronchoprovocation (provocative dose [PD20], 1.49 +/- 1.83 mu mol)

> but not

> with methacholine challenge. The detrimental effects of nebulized

GSH

> on the

> airway bronchial tone in patients with mild asthma strongly suggests

> bronchoconstriction provoked by sulfite formation. [References: 29]

> Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Gillissen A. Jaworska M. Orth M. Coffiner M. Maes P. App

EM.

> Cantin AM. Schultzewerninghaus G.

> Title NACYSTELYN, A NOVEL LYSINE SALT OF N-ACETYLCYSTEINE, TO

AUGMENT

> CELLULAR ANTIOXIDANT DEFENCE IN VITRO

> Sourc Respiratory Medicine. 91(3):159-168, 1997 Mar.

>

> Abstract Nacystelyn (NAL), a recently-developed lysine salt of N-

> acetylcysteine (NAC), and NAG, both

> known to have excellent mucolytic capabilities, were tested for

their

> ability to enhance cellular antioxidant defence mechanisms. To

> accomplish

> this, both drugs were tested in vitro for their capacity: (1) to

> inhibit

> O-2(-) and H2O2 in cell-free assay systems; (2) to reduce O-2(-)

and

> H2O2

> released by polymorphonuclear leukocytes (PMN); and (3) for their

> cellular

> glutathione (GSH) precursor effect. In comparison with GSH, NAL and

> NAC

> inhibited H2O2, but not O-2(-), in cell-free, in vitro test systems

> in a

> similar manner. The anti-H2O2 effect of these drugs was as potent

as

> that of

> GSH, an important antioxidant in mammalian cells. To enhance

cellular

> GSH

> levels, increasing concentrations (0-2 x 10(-4) mol l(-1)) of both

> substances were added to a transformed alveolar cell line (A549

> cells).

> After NAC administration (2 x 10(-4) mol l(-1)), total

intracellular

> GSH

> (GSH-t2GSSG) levels reached 4.5 +/- 1.1 x 10(-6) mol per 10(6)

cells,

> whereas NAL increased GSH to 8.3 +/- 1.6 x 10(-6) mol per 10(6)

> cells. NAC

> and NAL administration also induced extracellular GSH secretion;

about

> two-fold (NAG), and 1.5-fold (NAL), respectively. The GSH precursor

> potency

> of cystine was about two-fold higher than that of NAL and NAG,

> indicating

> that the deacetylation process of NAL and NAC slows the ability of

> both

> drugs to induce cellular glut production and secretion.

> Buthionine-sulphoximine, which is an inhibitor of GSH synthetase,

> blocked

> the cellular GSH precursor effect of all substances. In addition,

> these data

> demonstrate that NAC and NAL reduce H2O2 released by freshly-

isolated

> cultured blood PMN from smokers with chronic obstructive pulmonary

> disease

> (COPD) (n=10) in a similar manner (about 45% reduction of H2O2

> activity by

> NAC or NAL at 4 x 10(-6) mol l(-1)). In accordance with the results

> obtained

> from cell-free, in vitro assays, O-2(-) released by PMN was not

> affected.

> Ambroxol (concentrations: 10(-9)-10(-3) mol l(-1)) did not reduce

> activity

> levels of H2O2 and O-2(-) in vitro. Due to the basic effect of

> dissolved

> lysine, which separates easily in solution from NAL, the acidic

> function of

> the remaining NAC molecule is almost completely neutralized [at

> concentration 2 x 10(-4) M: pH 3.6 (NAC), PH 6.4 (NAL)]. Due to

their

> function as H2O2 scavengers, and due to their ability to enhance

> cellular

> glutathione levels, NAL and NAC both have potent antioxidant

> capabilities in

> vitro. The advantage of NAL over NAC is two-fold; it enhances

> intracellular

> GSH levels twice as effectively, and it forms neutral pH solutions

> whereas

> NAC is acidic. Concluding from these in vitro results, NAL could be

an

> interesting alternative to enhance the antioxidant capacity at the

> epithelial surface of the lung by aerosol administration.

> [References: 48]

> Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Gillissen A. Scharling B. Jaworska M. Bartling A. Rasche K.

> Schultzewerninghaus G.

> Title OXIDANT SCAVENGER FUNCTION OF AMBROXOL IN VITRO

> - A COMPARISON WITH N-ACETYLCYSTEINE

> Source Research in Experimental

> Medicine. 196(6):389-398, 1997 Mar.

>

> Abstract Highly reactive oxygen metabolites play an important role

in

> inflammatory processes in the lung.

> Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]

> benzylamine) has

> been shown to reduce oxidant-mediated cell damage. However, the

> mechanism of

> this effect remains unclear. In order to evaluate oxidant scavenger

> function

> increasing concentrations of ambroxol (0-10(-3) mol/l) were

compared

> with

> equimolar concentrations of N-acetylcysteine (NAG) and glutathione

> (GSH) in

> vitro to reduce OH. (hydroxyl radical), HOCl (hypochlorous acid), O-

2

> (-)

> (superoxide anion) and H2O2 (hydrogen peroxide). OH. was measured

> spectrophotometrically (deoxyribose assay); O-2(-) (xanthine/x-

> oxidase),

> H2O2 and HOCl (HOCI/OCl-) were determined by chemiluminescence.

> Ambroxol,

> NAC and reduced GSH scavenged OH. significantly at 10(-3) mol/l,

> while HOCl

> was inhibited at concentrations greater than or equal to 10(-4)

mol/l

> completely (P<0.01). NAC and GSH had no anti-O-2(-) function, while

> ambroxol

> (10(-4) mol/l) reduced O-2(-) by 14.3+/-6.7%. In contrast, GSH and

NAC

> scavenged H2O2 at >10(-6) mol/l (P<0.01), while ambroxol had no

anti-

> H2O2

> effect. Our data demonstrate direct oxidant-reducing capabilities of

> ambroxol, which may be directly related to the aromatic moiety of

the

> molecule. However, high concentrations (micromolar concentrations)

are

> needed. Due to differences in direct oxidant scavenger function, a

> combination of ambroxol and NAC could be beneficial in antioxidant

> therapy.

> [References: 38] Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Gillissen A. Wickenburg D. Vanzwoll D. Schultzewerninghaus

G.

> Title BETA-2-AGONISTS HAVE ANTIOXIDANT FUNCTION IN VITRO .2. THE

> EFFECT OF

> BETA-2-AGONISTS ON OXIDANT-MEDIATED CYTOTOXICITY AND ON SUPEROXIDE

> ANION

> GENERATED BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES

> Source Respiration. 64(1):23-28, 1997 Jan-Feb.

>

> Abstract Therapeutic agents which may be able to

> enhance the antioxidant screen of the epithelial surface of the

lung

> have

> the potential to influence the progression of lung inflammation.

This

> study

> evaluates the efficacy of a variety of antiasthma drugs to reduce

> oxidant-mediated cytotoxicity and to inhibit superoxide anion

> generated by

> human polymorphonuclear leukocytes. We quantified in vitro the

> prevention of

> H2O2-mediated cytotoxicity (lactate dehydrogenase release assay)

> using the

> antiasthma drugs as follows: ipratropium bromide, salbulamol

> (salbutamol

> base), fenoterol (fenoterol hydrobromide), terbutaline (terbutaline

> sulfate), isoproterenol, prednisolone (prednisolone

> hydrogensuccinate),

> beclomethasone (17,21-beclomethasone dipropionate) and reduced

> glutathione.

> Furthermore, fenoterol and isoproterenol were evaluated ex vivo to

> reduce

> superoxide anion (O-2(-)) generated by freshly isolated

> polymorphonuclear

> cells (PMN) from smokers with chronic obstructive lung disease (n =

> 10).

> Using a concentration of 10(-4)M reduction of cytotoxicity was quite

> different among beta(2)-agonists: fenoterol (97.8%) > isoproterenol

> (67.6%)

> > salbulamol (41.8%) > terbutaline (30.5%) > ipratropium bromide

> (18.1%).

> Corticosteroids and theophylline had no antioxidant effect. The

> cellular

> O-2(-) production of freshly isolated PMN was significantly (p <

0.05,

> comparisons O vs. greater than or equal to 10(-7) M) reduced with

> fenoterol

> and isoproterenol at concentrations greater than or equal to 10(-7)

M.

> Propranolol had no inhibitory effect on antioxidant properties of

> beta(2)-agonists. We hypothesize that the antioxidant function of

> beta(2)-agonists is related to the number and formation of hydroxyl

> groups

> of the phenol rings within their molecular structure. These results

> demonstrate that beta(2)-agonists have in part a good intrinsic

> scavenger

> function on reactive oxygen species when used in micromolar

> concentrations.

> However. to achieve this effect supratherapeutic concentrations were

> necessary. Thus, the conceivable benefit of beta(2)-agonists in the

> treatment of high oxidant burden in vivo seems doubtful.

[References:

> 39]

> Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Vogelmeier C. Gillissen A. Buhl R.

> Title USE OF SECRETORY LEUKOPROTEASE INHIBITOR TO AUGMENT LUNG

> ANTINEUTROPHIL ELASTASE ACTIVITY

> Source Chest. 110(6 Suppl S):S 261-S 266, 1996 Dec.

>

> Abstract Physiologically, secretory leukoprotease inhibitor (SLPI)

is

> the major

> antiprotease of the epithelium of the upper respiratory tract

> providing

> protection against neutrophil elastase (NE). The recombinant form

of

> SLPI

> (rSLPI) has several advantages compared with alpha(1)-antitrypsin

> that make

> it interesting as potential therapy. In vitro, rSLPI proves to be an

> excellent inhibitor of NE. When administered as an aerosol in vitro

> and in

> vivo, the structure and function of rSLPI remain intact. Using the

> aerosol

> route, the half-life of rSLPI in respiratory epithelial lining

fluid

> is 12

> h; thus, giving it twice daily should guarantee satisfactory levels

> in the

> lung. Following inhalation, rSLPI moves from the epithelium in an

> intact

> form into the interstitium of the lung. Following on from these in

> vitro and

> in vivo experiments, a short-term study in patients with cystic

> fibrosis was

> performed,vith aerosolized rSLPI. Promising results relative to NE

> level

> reduction and the consequences for the inflammatory process in the

> bronchi

> were achieved. rSLPI not only induced an increase of the anti-NE

> protective

> screen, but also improved the antioxidant protection by raising

> glutathione

> levels in the lung in sheep. rSLPI may therefore provide a unique

> opportunity for protecting the lung from the damage caused by

> inflammatory

> processes by giving a single drug. [References: 58] Publication

Type

> Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Buhl R. Meyer A. Vogelmeier C.

> Title OXIDANT-PROTEASE INTERACTION IN THE LUNG - PROSPECTS FOR

> ANTIOXIDANT THERAPY

> Source Chest. 110(6 Suppl S):S 267-S 272, 1996 Dec.

>

> Abstract

> In inflammatory lung

> disorders, oxidants and proteases complement each other in their

> potential

> to destroy lung parenchyma. It is therefore rational to combine

> therapeutic

> strategies aimed at augmenting the antiproteolytic defenses of the

> lung in

> diseases such as emphysema with antioxidant strategies. In the

> healthy lung,

> the oxidant burden is balanced by the local antioxidant defenses.

> However,

> both an increased oxidant burden and/or decreased antioxidant

> defenses may

> reverse the physiologic oxidant-antioxidant balance in favor of

> oxidants,

> leading to lung injury. This concept points to an obvious

therapeutic

> strategy: augmentation of the antioxidant screen of the lung to

> prevent

> oxidant-mediated tissue damage. Studies using reduced glutathione

> (GSH), the

> major pulmonary antioxidant, as a model therapeutic agent

> demonstrated that

> GSH can be administered directly to the respiratory epithelial

> surface by

> aerosol and is fully functional as an antioxidant both in vitro and

> in vivo.

> In pulmonary diseases such as idiopathic pulmonary fibrosis or

> following HN

> infection, GSH aerosol therapy not only normalized deficient

> pretherapy GSH

> levels in the lung, but was capable of favorably influencing

cellular

> events

> such as oxidant release by pulmonary inflammatory cells, The same

was

> true

> for oral antioxidant therapy with N-acetylcysteine, a glutathione

> precursor.

> These results suggest that it is possible to use antioxidants to

> reverse the

> imbalance between oxidants and antioxidants at the site of oxidant

> injury to

> prevent the progressive tissue damage in lung disorders

characterized

> by

> high oxidant states, Antioxidants, alone and in combination with

> antiproteases, merit further long-term studies for clinical therapy.

> [References: 57] Publication Type Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Bernorio S. Pecis M. Zucchi A. Guerra G. Migliorini V.

Negri

> L.

> Corsano A.

> Title GLUTATHIONE IN BRONCHIAL HYPERRESPONSIVENESS

> Source Journal

> of Aerosol Medicine-Deposition Clearance & Effects in the Lung.

> 9(2):207-213, 1996 Sum.

>

> Abstract Alterations of oxidants and antioxidants

> now appear to be pivotal in the development of bronchial

> hyperresponsiveness

> and bronchial asthma, To evaluate the potential protective role of

the

> antioxidant reduced glutathione (GSH) administered by ultrasonic

> nebulizer

> on metacholine-induced bronchoconstriction, we designed a double-

> blind,

> randomized study enrolling 18 subjects,vith mild asthma and previous

> bronchoconstriction after a methacholine challenge; we did not find

a

> statistically significant decrease in bronchoconstriction after

> premedication with inhaled GSH, Further investigation under

different

> experimental conditions is warranted because our information about

> the mode

> of action and pharmacokinetics of GSH is still incomplete and

> sometimes the

> data are conflicting. [References: 19] Publication Type Article

>

> http://www.thorne.com/n_acetylcysteine.html :

> Significance of glutathione in lung disease and implications for

> therapy.

> Glutathione is a tripeptide that contains an important thiol

> (sulfhydryl)

> group within the central cysteine amino acid. Glutathione is

involved

> in

> numerous vital processes where the reducing potential of the thiol

is

> used.

> Several lung disorders are believed to be characterized by an

> increase in

> alveolar oxidant burden, potentially depleting alveolar and lung

> glutathione. Low glutathione has been linked to abnormalities in

the

> lung

> surfactant system and the interaction between glutathione and

> antiproteases

> in the epithelial lining fluid of patients. Normal levels of

> intracellular

> glutathione may exert a critical negative control on the

elaboration

> of

> proinflammatory cytokines. The increase of intracellular reactive

> oxygen

> species is believed to correlate with the activation of NF-kappa B,

a

> strongly implicate free radical injury in the genesis and

maintenance

> of

> several lung disorders in humans. This information is substantial

and

> will

> help the development of clinical studies examining a variety of

> inflammatory

> lung disorders. PE;Bernard GR. Significance of glutathione in

> lung

> disease and implications for therapy. Am J Med Sci 307:119-127;1994

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Lands LC. Grey V. Smountas AA. Kramer VG. McKenna D.

> Title Lymphocyte glutathione levels in children with cystic

fibrosis

> Source Chest. 116(1):201-205, 1999 Jul.

>

> Abstract

> Objective: Lung disease in cystic fibrosis (CF) is characterized

by

> a

> neutrophilic inflammatory response. This can lead to the production

of

> oxidants, and to oxidative stress in the lungs. Glutathione (GSH)

> represents

> the primary intracellular antioxidant, and provides an important

> defense in

> the epithelial lining fluid. Evidence suggests that lymphocyte GSH

> reflects

> lung GSH concentrations, and so could potentially serve as a

> peripheral

> marker of lung inflammation.

>

> Methods: We assessed peripheral blood lymphocyte GSH

concentrations

> in 20

> children (13 boys) with CF who were in stable condition at the time

of

> evaluation. Values were compared with nutritional status and lung

> function

> parameters.

>

> Results: Patients were 11.7 +/- 3.03 years old (mean +/- SD).

Their

> percentage of ideal body weight was 101.8 +/- 17.92%; FEV1, 79.5 +/-

> 19.22%

> predicted; FEV1/FVC, 75.0 +/- 10.08%; and residual volume

(RV)/total

> lung

> capacity (TLC), 31.3 +/- 10.47%. For the group, the GSH

concentration

> was

> 1.31 +/- 0.52 mu mo/10(6) lymphocytes, which was not different from

> laboratory control values. GSH values were correlated with

nutritional

> status (percentage of ideal body weight: r = 0.49, p < 0.03) and

the

> degree

> of gas trapping (RV/TLC: r = 0.50, p < 0.03), and were correlated

> inversely

> with airflow limitation (FEV1, percent predicted: r = -0.45, p <

0.05;

> FEV1/FVC: r = -0.48 is, p < 0.04), but not with age, height, or

> weight (p >

> 0.1).

>

> Conclusions: We interpret the inverse correlation between

> lymphocyte GSH

> concentration and lung function as a reflection of upregulation of

GSH

> production by lung epithelial tissue in response to oxidative

stress.

> We

> interpret the correlation between lymphocyte GSH concentration and

> nutritional status as a reflection of the role of cysteine in

hepatic

> glutamine metabolism. Peripheral blood lymphocyte GSH concentration

> may

> potentially serve as a convenient marker of lung inflammation.

> Furthermore,

> the increased demand for GSH production in the face of ongoing

> inflammation

> suggests a potential role for supplementation with cysteine donors.

> [References: 39]

> Publication Type

> Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Roum JH. Borok Z. McElvaney NG. Grimes GJ. Bokser AD.

> Buhl R. Crystal RG.

> Title Glutathione aerosol suppresses lung epithelial surface

> inflammatory cell-derived oxidants in cystic fibrosis

> Source Journal of Applied Physiology. 87(1):438-443, 1999 Jul.

>

> Abstract

> Cystic fibrosis (CF) is characterized by accumulation of activated

> neutrophils and macrophages on the respiratory epithelial surface

> (RES);

> these cells release toxic oxidants, which contribute to the marked

> epithelial derangements seen in CF. These deleterious consequences

are

> magnified, since reduced glutathione (GSH), an antioxidant present

in

> high

> concentrations in normal respiratory epithelial lining fluid (ELF),

is

> deficient in CF ELF. To evaluate the feasibility of increasing ELF

GSH

> levels and enhancing RES antioxidant protection, GSH aerosol was

> delivered

> (600 mg twice daily for 3 days) to seven patients with CF. ELF

total,

> reduced, and oxidized GSH increased (P < 0.05, all compared with

> before GSH

> therapy), suggesting adequate RES delivery and utilization of GSH.

> Phorbol

> 12-myristate 13-acetate-stimulated superoxide anion (O-2(-).)

release

> by ELF

> inflammatory cells decreased after GSH therapy (P < 0.002). This

> paralleled

> observations that GSH added in vitro to CF ELF inflammatory cells

> suppressed

> O-2(-). release (P < 0.001). No adverse effects were noted during

> treatment.

> Together, these observations demonstrate the feasibility of using

GSH

> aerosol to restore RES oxidant-antioxidant balance in CF and

support

> the

> rationale for further clinical evaluation. [References: 45]

> Publication Type

> Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Gao L. Kim KJ. Yankaskas JR. Forman HJ.

> Title Abnormal glutathione transport in cystic fibrosis airway

> epithelia

> Source American Journal of Physiology - Lung Cellular & Molecular

> Physiology.

> 21(1):L113-L118, 1999 Jul.

>

> Abstract

> Glutathione (GSH) is a potentially important component of

> antioxidant

> defense in the epithelial lung lining fluid. Cystic fibrosis (CF)

> patients

> have chronic inflammation in which oxidative stress can be a

factor.

> To

> examine the hypothesis that the transport of GSH content was

> defective in CF

> patients, intracellular and extracellular GSH were measured by

HPLC.

> Four

> cell lines were used: CFT1 cells [with defective CF transmembrane

> conductance regulator (CFTR), Delta F508 homozygous, two clones]

and

> one of

> the CFT1 clones transfected with either normal CFTR (CFTR repleted)

or

> beta-galactosidase. GSH content in the apical fluid was 55% lower in

> CFTR-deficient cultures than in CFTR-repleted cells (P < 0.001). In

> contrast, intracellular GSH content was similar in CFT1 cells and

> CFTR-repleted cells. gamma-Glutamyl transpeptidase activity, which

> degrades

> extracellular GSH, did not account for differences in apical GSH.

> Rather,

> GSH efflux of CFTR-deficient cells was lower than that of CFTR-

> repleted

> cells. These studies suggested that decreased GSH content in the

> apical

> fluid in CF resulted from abnormal GSH transport associated with a

> defective

> CFTR. [References: 28]

> Publication Type

> Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Linsdell P. Hanrahan JW.

> Title GLUTATHIONE PERMEABILITY OF CFTR

> Source American Journal of Physiology - Cell Physiology. 44(1):C

323-

> C 326, 1998 Jul.

>

> Abstract

> The cystic fibrosis transmembrane conductance regulator (CFTR)

> forms an

> ion channel that is permeable both to Cl- and to larger organic

> anions. Here

> we show, using macroscopic current recording from excised membrane

> patches,

> that the anionic antioxidant tripeptide glutathione is permeant in

> the CFTR

> channel. This permeability may account for the high concentrations

of

> glutathione that have been measured in the surface fluid that coats

> airway

> epithelial cells. Furthermore, loss of this pathway for glutathione

> transport may contribute to the reduced levels of glutathione

> observed in

> airway surface fluid of cystic fibrosis patients, which has been

> suggested

> to contribute to the oxidative stress observed in the lung in cystic

> fibrosis. We suggest that release of glutathione into airway

surface

> fluid

> may be a novel function of CFTR. [References: 21]

> Publication Type

> Article

>

>

> --------------------------------------------------------------------

--

> ----------

> Authors Grimble RF.

> Title MODIFICATION OF INFLAMMATORY ASPECTS OF IMMUNE FUNCTION BY

> NUTRIENTS

> Source Nutrition Research. 18(7):1297-1317, 1998 Jul.

>

> Abstract

> The pro-inflammatory cytokines interleukin 1 (IL1) interleukin 6

> (IL6) and

> tumour necrosis factor-alpha (TNF), and reactive oxygen species

> (ROS), play

> a-major role in inflammatory aspects of immune function. They are

> closely

> linked with pathology in a wide range of diseases and condition

which

> have

> an inflammatory basis. Alterations in the intake of fats,

antioxidant

> nutrients, protein and specific amino acids change many aspects of

> inflammation by interacting with cytokine and ROS biology, thereby

> providing

> a means of modulating inflammation. Mortality and morbidity, in a

> diverse

> range of diseases, have been linked with excessive or untimely

> oxidant and

> pro-inflammatory cytokine production. Evidence of oxidative damage

> has been

> observed in sepsis, HIV and hepatitis infection, cancer, diabetes

> mellitus,

> alcoholic liver disease and cystic fibrosis. ROS produced during the

> inflammatory response enhances pro-inflammatory cytokine production

by

> activation of nuclear factor kappa B (NF kappa . The interaction

is

> an

> important part of the up-regulation of inflammatory aspects of

immune

> function. The interaction between ROS and cytokines has the

potential

> to

> damage the host but is held in check by the antioxidant defences.

> Nutrient

> intake directly and indirectly influences antioxidant defence.

> Glutathione

> is a major endogenous antioxidant and is important for lymphocyte

> replication. Vitamin B, and riboflavin participate in the

maintenance

> of

> glutathione status. Vitamin B, acts as a cofactor in the synthesis

of

> cysteine (the rate limiting precursor for glutathione biosynthesis)

> and

> riboflavin is a cofactor for glutathione reductase. Deficiencies in

> vitamins

> E, B, and riboflavin reduce cell numbers in lymphoid tissues of

> experimental

> animals and produce functional abnormalities in the cell mediated

> immune

> response. Sulphur amino acid deficient rats exhibit an impaired

> ability to

> synthesise glutathione during inflammation and have increased

numbers

> of

> neutrophils in lung. Ascorbic acid and tocopherols exert anti-

> inflammatory

> effects in studies in man and animals. In humans, dietary

> supplementation

> with ascorbic-acid, tocopherols and vitamin B, enhances a number of

> aspects

> of lymphocyte function-In smokers indices of inflammation inversely

> relate

> to the intakes of vitamins C and E. Studies in healthy subjects,

> patients

> and experimental animals clearly demonstrate that unsaturated fats

> modulate

> pro-inflammatory cytokine biology. In general n-6 polyunsaturated

> fatty

> acids enhance, and n-3 PUFAs and monounsaturated fatty acids

suppress,

> cytokine mediated aspects of inflammation. In addition, n-6 PUFAs

and

> cholesterol enhance and n-3 PUFAs suppress cytokine production.

Fats

> rich in

> n-3 PUFAs are efficacious in a number of inflammatory diseases,

> however in

> smokers indices of inflammation are enhanced in subjects consuming

> greater

> than 5% of dietary energy in the form of n-6 PUFAs. Fats may

modulate

> cytokine biology by a number of mechanisms closely linked to

membrane

> phospholipid composition. As a consequence of diet induced change,

> alterations in prostaglandin, leukotriene and diacyl glycerol

> production,

> protein kinase C activation and fluidity may occur. Recent studies

> suggest

> that changes in bulk membrane fluidity are unlikely to underlie the

> substantial modulatory effects of fats on cytokine biology.

>

> In conclusion nutrients have a major potential for modulating

> inflammatory

> aspects of immune function due to interaction with three main areas

> whereby

> inflammation is prosecuted and controlled. Firstly by changing

> provision of

> substrate for the synthesis of molecules for components for the

> executive

> and control systems (protein, sulphur amino acids, glutamine).

>

> Secondly by modulating the composition of the membranes of cells

> involved

> in the inflammatory process (unsaturated fatty acids and

cholesterol)

> and

> thirdly by influencing the interaction between ROS and NF kappa B

> activation

> (sulphur amino acids, vitamins C and E, and riboflavin). © 1998

> Elsevier

> Science Inc. [References: 130]

> Publication Type

> Review

> Funded Pilot Projects - Abstracts

> Year 6: April 1, 2000-March 31, 2001

>

> Role of Glutamate-L-cysteine Ligase in Cystic Fibrosis

> Terrance J. Kavanagh, PhD, Associate Professor,

> Department of Environmental Health, UW

> Cystic fibrosis is a debilitating systemic disorder that affects the

> lungs, the pancreas and the intestine. Most CF is thought to be due

> to a mutation in the cystic fibrosis transmembrane regulator protein

> (CFTR0. However, other factors certainly contribute the severity and

> progression of this disease. Recently, it has been shown that CFTR

> may influence the ability of airway epithelial cells to transport

the

> antioxidant glutathione. Glutathione is important in preserving lung

> function in the face of oxidative stress, which is a frequent

> occurrence in CF. Individuals with CF have been shown to have lower

> levels of GSH in their alveolar lining fluid. This suggests that CF

> may be characterized by an inability to supply the alveolus with

> sufficient GSH. We have recently shown that a polymorphism in the

GSH

> biosynthetic enzyme glutamate-L-cysteine ligase (GLCL) is associated

> with risk for idiopathic pulmonary fibrosis, a condition that also

is

> characterized by low GSH in the alveolar lining fluid. The aims of

> this proposal are to examine the prevalence of the GLCL polymorphism

> in CF patients, and to assess the association of various alleles

with

> disease severity. This information will help to define the

> variability in disease severity seen in this condition and also lead

> to rational antioxidant therapy for these patients.

>

>

>

>

>

> This website contains cystic fibrosis research. This research

> explores how to correct the condition of cystic fibrosis. The

> remedies for cystic fibrosis mentioned on this site are

hypothetical

> and untested. SharkTank Research International does not suggest,

> recommend, imply or, in any way, advise you to undertake any remedy

> mentioned on this website without your medical professional's

> supervision and consent.