Abstracts
Aerobic PerformanceAging & Cancer
Aging & Cancer
The incidence and mortality rates from most cancers increase exponentially with age (peaking between 50 and 70 years). One factor, in an increased susceptibility to neoplasia, is a deficiency in GSH.
This deficiency is due to a lack of the precursor amino acid, cysteine. A causal role was suggested, for GSH deficiency, by increased longevity accruing from feeding with a cysteine precursor.
Richie, J.P. : The role of glutathione in aging and cancer.
Breast Cancer (Glutathione)
Breast Cancer
Glutathione concentration is high in most tumor cells which may be important in resistance to chemotherapy.
Whey protein concentrate appeared to deplete tumor cells of GSH and render them more vulnerable to chemotherapy.
Kennedy, R.S. et al., The use of whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I - II clinical study. Anticancer Research, 1995, 15: 2,643-2,650.
Malnutrition (Glutathione)
Malnutrition
It has been demonstrated that:
(1) decreased tissue GSH is associated with increased toxicity and disease;
(2) supplementation concomitant with exposure to an oxidative challenge reduces toxicity or disease.
It has been proposed that GSH (or GSH precursors i.e. NAC) be used therapeutically for human diseases which are free radical mediated and deplete GSH stores e.g. alcoholism, HIV (AIDS), Parkinson's and respiratory distress syndrome.
Malnutrition contributes to morbidity and mortality in many diseases, including alcoholism, AIDS and cancer.
Many other diseases, while not caused by free radical overload, initially, require oxygen and drug therapies which can increase oxidative stress.
For our studies, hyperoxia exposure (85%) provided oxidative stress. A cysteine pro-drug was used: OTC (oxothiazoline-carboxylate).
OTC supplementation protected both malnourished rats from pulmonary oxygen toxicity and adequately nourished rats exposed to hyperoxia.
Bray, T.M. & Taylor, C.G.: Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochem. Phar, 1994, 47(12): 2,113-2,123.
Cystic Fibrosis & Glutathione
Cystic fibrosis
Glutathione (GSH) aerosol may improve respiratory epithelial surface (RES)in cystic fibrosis (CF) patients. Glutathione, an antioxidant found in normal respiratory epithelial lining fluid (ELF), is lacking in CF patients. According to this study, seven CF patients were treated with GSH aerosols (600mg.) in order to determine the antioxidant effect of the agent. Increasing levels of ELF total, reduced, and oxidized GSH were found after treatment. Thus, glutathione may be used to treat cystic fibrosis patients.
Roum JH, Borok Z, McElvaney NG, Grimes GJ, Bokser AD, Buhl R, Crystal RG: Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis, J Appl Physiol 1999 Jul; 87(1): 438-443
Glutathione Deficiency
Glutathione deficiency
According to these studies, a decreased level of glutathione (GSH) in the apical fluid may be found among cystic fibrosis patients. The decrease may be due to abnormal GSH transport. To study possible abnormal GSH transport in CF patients, intracellular and extracellular GSH were examined. The researchers found that GSH levels in the apical fluid improved if the cells had been treated with CF transmembrane conductance regulator. Hence, deficiency in glutathione levels in apical fluid may have an impact on cystic fibrosis patients. Thus, glutathione agents may be beneficial in CF treatment.
Gao L, Kim KJ, Yankaskas JR, Forman HJ: Abnormal glutathione transport in cystic fibrosis airway epithelia, Am J Physiol 1999 Jul; 277(1 Pt 1): L113-L118
Allylamine
Allylamine
Glutathione S-transferases (GST) may act as an important defense against allylamine (AA), a cardiovascular toxin that causes lesions similar to atherosclerosis. In these studies, the effects of semicarbazide sensitive amine oxidase (SSAO) on AA were observed in cultured rat vascular smooth muscle cells (VSMC). Pretreatment with a GST inhibitor increased AA toxicity, indicated that GST may have a protective effect against AA.
He N, Singhal SS, Awasthi S, Zhao T, Boor PJ: Role of Glutathione S-transferase 8-8 in Allylamine Resistance of Vascular Smooth Muscle Cells in Vitro, Toxicol Appl Pharmacol 1999 Jul 15; 158(2): 177-185
Hypertension & Glutathione
Hypertension
Glutathione both in vivo and in vitro may directly increase intracellular magnesium and correlate with glucose metabolism. According to this study, glutathione was examined on red blood cell intracellular magnesium in both hypertensive and healthy patients. In vivo infusions of glutathione raised RBC-Mg in both groups of patients. Increased level of Mg was found in GSH (in vitro).
Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G: Effects of glutathione on red blood cell intracellular magnesium : relation to glucose metabolism, Hypertension 1999 Jul; 34(1):76-82
Parasites (Glutathione)
Parasites
Glutathione may act as a protective barrier against nitric oxide cytotoxicity in both macrophages and parasites. In this study, effects of glutathione against NO cytotoxicity in macrophage and Leishmania major glutathione were examined. Buthionine sulfoximine (BSO), an enzyme inhibitor, created an irreversible depletion of macrophage glutathione and a 20% reversible decrease in l. major glutathione. The glutathione-depleted macrophages released 60% less NO than did the untreated macrophages. Therefore, a correlation may exist between the levels of glutathione and nitric oxide cytotoxicity.
Romao PR, Fonseca SG, Hothersall JS, Noronha-Dutra AA, Ferreira SH, Cunha FQ: Glutathione protects macrophages and Leishmania major against nitric oxide-mediated cytotoxicity, Parasitology 1999 Jun; 118 (Pt 6): 559-66
AIDS (Glutathione)
AIDS
"AIDS" may be the consequence of a "virus"-induced cysteine deficiency. HIV-"infected" persons have markedly decreased plasma cystine and cysteine concentrations, decreased "intracellular" glutathione and elevated plasma glutathione levels.
Propose consideration of NAC for the treatment of these patients.
Recent studies have indicated that excessive T "cell" stimulation increases "nutritional" requirements and causes a temporary decrease of "intracellular" glutathione levels, unless met by supplements of cysteine or glutathione.
HIV patients with high plasma cystine and low plasma glutamate levels have higher CD4+ T "cell" counts than other sub-groups.
The "antioxidant", cysteine, can be prooxidative (facilitating "oxidative" processes) simply by being a precursor for the oxidizing compound, glutathione disulfide (GSSG).
The correlation between cysteine and CD4+ T cell counts also held for healthy individuals.
Dorge, W. et al., Abnormal redox regulation in HIV "infection" and other immunodeficiency diseases. In: Pasquier et al., (eds) ""Oxidative" "Stress", Cell Activation and "Viral Infection"". Birkhauser Verlag, Basel. 1994.
Mice, fed undenatured (i.e. from non-pasteurized milk) dietary "whey" "protein" concentrate, exhibited higher levels of tissue glutathione.
The humoral "immune" response was also significantly higher (counting the number of "plaque"-forming cells responding to sheep "red blood cells".
Bounous, G. & Gold, P.: The biological activity of undenatured dietary "whey" "proteins": role of glutathione. Clin. Invest. Med. 1991,14(4): 296-305.
Brussels Sprouts
Brussels Sprouts
Brussels sprouts consumption has been linked with decreased "cancer" risk. This study attempted to identify the underlying mechanism, possibly glutathione S-transferase (GST).
Brussels sprouts did increase rectal levels of GST-alpha and -pi isozyme levels. These enhanced detoxification "enzyme" levels may partly explain the epidemiological association between a high intake of glucosinolates (cruciferous vegetables) and a decreased risk of colorectal cancer.
Nijhoff, W.A. et al: Effects of consumption of Brussels sprouts on intestinal and "lymphocytic" glutathione S-transferase in humans. Carcinogenesis, 1995, 16(9): 2,125-2,128.
Prostate Cancer & Glutathione
Prostate Cancer
Prostate cancer is associated with "aging" and may reflect a more oxidative state. This study used established "carcinoma" cell lines and measured the balance between oxidative states (induced by androgen exposure) and antioxidant defense mechanisms (e.g. the glutathione system).
Reactive oxygen species, "lipid" peroxides and catalse activity, were elevated by physiologically relevant levels of androgens (e.g. DHT).
This brought about a decrease of glutathione levels.
It has already been shown that another antioxidant, "lycopene" provides protection against prostate cancer.
Ripple, M.O. et al., Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. J. Ntnl. Cancer Inst. 1997, 89(1): 40-48.
Renal Failure
Renal Failure
A profound imbalance between oxidants and "antioxidants" has been suggested in uremic patients on maintenance "hemodialysis" that could contribute to accelerated "atherosclerosis" and other long-term complications.
Circulating levels of "copper"-"zinc" "superoxide dismutase", glutathione peroxidase and reductase were determined.
Erythrocyte levels of glutathione increased, while total glutathione levels and glutathione peroxidase activity decreased.
Ceballos-Picot, I. et al: Glutathione antioxidant system as a marker of oxidative stress in chronic "renal failure". Free Radical Biol. Med. 1996, 21(6): 845-853.
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