iThyroid.com

GLUTATHIONE

Glutathione (GSH) is a tripeptide formed from glutamic acid, cysteine, and glycine. Combined with vitamin E and selenium, glutathione forms glutathione peroxidase (GPx) which is one of the key antioxidants that protects the body and is critical for protection of the thyroid gland from oxidation damage.

 

Low levels of glutathione (along with low levels of vitamin E and selenium) may be a factor in the genesis of thyroid disease. Excessive intake of sugars and starches may reduce glutathione and thereby damage the thyroid gland.

 

Title

Role of the hepatic xanthine oxidase in thyroid dysfunction: effect of thyroid hormones in oxidative stress in rat liver.

Author

Huh K; Kwon TH; Kim JS; Park JM

Address

Department of Pharmacology, College of Pharmacy, Yeungnam University, Gyongsan, Korea.

Source

Arch Pharm Res, 21(3):236-40 1998 Jun

Abstract

Title

The effect of methimazole on the oxidant and antioxidant system in patients with hyperthyroidism.

Author

Ademo¨glu E; G¨okku¸su C; Yarman S; Azizlerli H

Address

Department of Biochemistry, Istanbul Faculty of Medicine, University of Istanbul, Turkey.

Source

Pharmacol Res, 38(2):93-6 1998 Aug

Abstract

The present study was designed to evaluate the changes in the plasma lipid peroxidation and antioxidant system in 15 adult volunteer patients in hyperthyroid and euthyroid states. In these patients, plasma concentrations of lipid peroxides were decreased and, ascorbic acid and vitamin E levels were significantly increased in euthyroid status in comparison to hyperthyroid status. A significant increase in the plasma GPx activity (P < 0.01) and a decrease in GST (P < 0.001) was observed after euthyroidism was sustained with methimazole therapy. In conclusion, hyperthyroidism tends to enhance lipid peroxide content and an increase in GST and decreases in GPx, vitamin E and ascorbic acid levels accompany to this change in the plasma. The achievement of euthyroidism led an improvement in these parameters.

 

This study shows that iron supplementation can increase the production of glutathione and glutathione peroxidase.

 

Title

The effect of iron supplementation on GSH levels, GSH-Px, and SOD activities of erythrocytes in L-thyroxine administration.

Author

Seymen O; Seven A; Candan G; Yigit G; Hatemi S; Hatemi H

Address

Department of Physiology, Cerrahpasa Medical Faculty, Istanbul University, Turkey.

Source

Acta Med Okayama, 51(3):129-33 1997 Jun

Abstract

Our aim was to study the effect of iron supplementation on the following aspects of erythrocyte metabolism in experimental hyperthyroidism: glutathione (GSH) levels, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities. Hyperthyroidism induced by L-thyroxine administrations significantly raised erythrocyte GSH, GSH-Px and SOD levels of the rats (P < 0.001). Likewise, we observed that iron supplementation induced significant rises in erythrocyte GSH, GSH-Px and SOD levels (P < 0.001) as compared with the control group. The erythrocyte GSH, GSH-Px and SOD levels of hyperthyroidism-induced iron-supplemented animals were significantly higher when compared with either the iron-supplemented group (P < 0.001) or the only L-thyroxine-administered hyperthyroid group (P < 0.001, P < 0.05, P < 0.01, respectively). The results of this study show that L-thyroxine administration and/or iron supplementation increases GSH, GSH-Px and SOD levels of erythrocytes.

 

Title

Copper-glutathione complexes under physiological conditions: structures in solution different from the solid state coordination.

Author

Pederson JZ; Steink¨uhler C; Weser U; Rotilio G

Address

Department of Biology, University of Rome Tor Vergata, Italy.

Source

Biometals, 9(1):3-9 1996 Jan

Abstract

The physiologically important copper complexes of oxidized glutathione have been examined by electron spin resonance (ESR) spectroscopy in aqueous solution at neutral pH. Low temperature measurements show that the Cu(II) binding site in oxidized glutathione has the same ligand arrangement as in copper complexes of S-methylglutathione, glutamine, glutamate and glycine. The site is composed of the amino nitrogens and the carboxyl oxygens of two gamma-glutamyl residues; there is no interaction with amide nitrogens, the sulphur bond or the glycyl carboxyl groups. At high metal to ligand ratios a binuclear species exists, in which each Cu(II) binds only to one gamma-glutamyl residue. The previously reported forbidden transition detected at g = 4 is due to non-specific aggregation and not to spin coupling of intramolecular sites. Liquid solution ESR spectra show the Cu(II)-glutathione complex has a lower mobility than the corresponding Cu(II)-S-methylglutathione species. From the degree of spectral anisotropy the complex with glutathione is calculated to exist as a dimer. These results demonstrate that the physiologically relevant complex between copper and oxidized glutathione in solution is completely different from the known solid state structure determined by crystallography.

Title

Role of cytosolic copper, metallothionein and glutathione in copper toxicity in rat hepatoma tissue culture cells.

Author

Steinebach OM; Wolterbeek HT

Address

Department of Radiochemistry, Delft University of Technology, The Netherlands.

Source

Toxicology, 92(1-3):75-90 1994 Sep 6

Abstract

Effects of metallothionein (MT) synthesis inhibiting compounds (actinomycin D, cycloheximide), MT synthesis stimulating compounds (dexamethasone, dibu-cAMP) and interfering metals (Cd, Zn) on copper accumulation were investigated in rat hepatoma tissue culture cells. Copper-metallothionein (Cu-MT) and MT-associated copper levels were determined to find a possible correlation between cytosolic copper concentrations and MT as a Cu-detoxifying protein. Further, intracellular non-MT associated copper levels and levels of GSH and SOD were determined. Cell viability was tested under all experimental conditions by measuring LDH-release, K+ uptake and total cell protein. Administration of dexamethasone and dibu-cAMP showed no effect on MT levels (compared with controls), and only a marginal effect on 64Cu and total Cu accumulation. Administration of actinomycin D resulted in increased copper accumulation in the particulate fraction, possibly due to inhibition of copper secretion processes and/or protein synthesis. Presence of zinc had no effect on MT levels nor on total Cu and 64Cu levels, in contrast with cadmium which drastically enhanced copper accumulation and MT levels in the cells. Cu/MT ratios varied from 1.0 +/- 0.3 to 3.3 +/- 1.2, which is far below the assumed maximum molar ratio of 8-12 mol Cu per mol MT. SOD levels appeared to be enhanced up to 2- or 3-fold in the presence of Cd2+, relative to control values. The role of GSH as Cu-intermediate in intracellular Cu distribution plus its role in copper defence mechanism(s) was tested by application of BSO, an inhibitor of GSH synthesis. It was found that BSO had no effect on intracellular MT level; it was found however that MT-bound copper levels were markedly decreased. The results presented support a model for copper metabolism in hepatoma tissue culture (HTC) cells, where Cu(I) is complexed by GSH immediately after entering the cell. GSH is capable of transferring copper to MT where it is stored. Depletion of GSH (by administration of Cd2+, actinomycin D, cycloheximide) almost instantaneously results in enhanced cellular toxicity. When also MT is depleted (by actinomycin D) non-MT associated, 'free' cytosolic Cu2+ is elevated, and HTC cells rapidly loose their resistance to copper toxicity, as also reflected in loss of cell viability (LDH, K+ and total cell protein).

Title

The role of glutathione in copper metabolism and toxicity.

Author

Freedman JH; Ciriolo MR; Peisach J

Address

Institute for Structural and Functional Studies, University City Science Center, Philadelphia, Pennsylvania 19140.

Source

J Biol Chem, 264(10):5598-605 1989 Apr 5

Abstract

Cellular copper metabolism and the mechanism of resistance to copper toxicity were investigated using a wild type hepatoma cell line (HAC) and a copper-resistant cell line (HAC600) that accumulates copper and has a highly elevated level of metallothionein (MT). Of the enzymes involved in reactive oxygen metabolism, only glutathionine peroxidase was elevated (3-4-fold) in resistant cells, suggestive of an increase in the cellular flux of hydrogen peroxide. A majority of the cytoplasmic copper (greater than 60%) was isolated from both cell lines as a GSH complex. Kinetic studies of 67Cu uptake showed that GSH bound 67Cu before the metal was complexed by MT. Depletion of cellular GSH with buthionine sulfoximine inhibited the incorporation of 67Cu into MT by greater than 50%. These results support a model of copper metabolism in which the metal is complexed by GSH soon after entering the cell. The complexed metal is then transferred to MT where it is stored. This study also indicates that resistance to metal toxicity in copper-resistant hepatoma cells is due to increases in both cellular GSH and MT. Furthermore, it is suggested that elevated levels of GSH peroxidase allows cells to more efficiently accommodate an increased cellular hydrogen peroxide flux that may occur as a consequence of elevated levels of cytoplasmic copper.

J Endocrinol Invest 1993 Apr;16(4):265-70

Acute iodine ingestion increases intrathyroidal glutathione.

Allen EM

Department of Medicine, University of Maryland Medical School, Baltimore.

In genetically predisposed individuals, autoimmune lymphocytic thyroiditis (LT) is potentiated by excess dietary iodine (I). There have been data which suggest that oxidative stress may have a role in iodine-induced LT. These in vivo studies were undertaken to examine the effect of iodine on intrathyroidal levels of the potent antioxidant glutathione (GSH) and see if the thyroids of LT-prone BB/Wor rats have aberrant GSH responses after iodine-loading. LT-prone BB/Wor, non LT-prone BB/Wor and Wistar rats were randomized to receive either 0.05% I (as Nal) or tap water. Thyroid and liver homogenates were assayed individually for GSH. Following the administration of 0.05% iodine water overnight, all of the animals demonstrated a rise in intrathyroidal GSH regardless of LT-proneness. To determine whether this was a dose-dependent response, Wis rats were randomized to receive tap, 0.0125%, 0.025%, 0.05%, or 0.075% I, overnight. Intrathyroidal GSH levels rose with increasing iodine concentrations peaking at 0.025% I. Hepatic GSH levels were unaltered by iodine treatment. Ten days of 0.05% I water did not result in any difference between the GSH levels of thyroids from treated and control rats. Frozen sections of the thyroids and livers from iodine-treated rats were compared to tap-water controls after staining with Mercury Orange for GSH and Schiff's reagent for evidence of lipid peroxidation. Iodine-treated thyroids had an apparent shift of GSH staining from the apical border to the cytoplasm. However, there was no Schiff's staining indicative of lipid peroxidation in the iodine-treated thyroids.

PMID: 7685786, UI: 93294146

 

Title

Hepatic glutathione biosynthetic capacity in hyperthyroid rats.

Author

Fern´andez V; Videla LA

Address

Departamento de Bioqu´imica, Facultad de Medicina, Universidad de Chile, Santiago-7, Chile.

Source

Toxicol Lett, 89(2):85-9 1996 Dec 16

Abstract

The influence of hyperthyroidism on the capacity of the liver to synthesize glutathione (GSH) was evaluated as a possible mechanism of depletion of the tripeptide. For this purpose, the effect of daily doses of 0.1 mg 3, 3',5-tri-iodothyronine (T3)/kg for 3 consecutive days on hepatic GSH biosynthetic capacity was assessed by a combined assay measuring gamma-glutamylcysteinyl synthase and GSH synthase simultaneously. T3 treatment induced a significant 56% depletion of liver GSH in parallel with an increase in the rate of GSH synthesis, the latter effect being completely abolished by L-buthionine sulfoximine. According to these data, the fractional rate of hepatic GSH turnover exhibited a 3.2-fold enhancement in hyperthyroid rats compared to control animals. It is concluded that the enhanced GSH utilization in the liver of hyperthyroid rats previously observed [Fern´andez et al., Endocrinology 129, 85-91, 1991], is accompanied by an increment in GSH synthesis that is insufficient to sustain the basal levels of the tripeptide observed in euthyroid animals, thus establishing a low steady-state content of GSH in the tissue.

 

Title

Glucose may induce cell death through a free radical-mediated mechanism.

Author

Donnini D; Zambito AM; Perrella G; Ambesi-Impiombato FS; Curcio F

Address

Dipartimento di Patologia e Medicina Sperimentale e Clinica, University of Udine Medical School, Italy.

Source

Biochem Biophys Res Commun, 219(2):412-7 1996 Feb 15

Abstract

It has been reported that glucose may autooxidize generating free radicals which have been hypothesized to induce important cellular abnormalities. To investigate the cell damage induced by glucose-dependent oxidative stress, the FRTL5 cell strain was incubated in 10 or 20 mM glucose, either alone or in the presence of buthionine-sulfoximine, a transition state inhibitor that blocks glutathione synthesis. We found indeed that buthionine-sulfoximine greatly inhibited glutathione production and increased malondialdehyde (a marker of oxidative cell damage) levels, especially in 20mM glucose. We also found that, when glutathione production was inhibited, 10mM glucose induced apoptosis and 20 mM glucose induced necrosis. These data show that the glucose-dependent cell damage is a function of glutathione production. They also show that such glucose-dependent free radical production may be critical for determining cell damage, even for small variations as the ones we tested (from 10 to 20 mM glucose).

Following is an article from Dr. Mercola's website, mercola.com, which talks about how high blood sugar can decrease glutathione and increase malonaldehyde, which can damage the thyroid and pancreas.

Lowering Blood Sugar Raises Glutathione and Vitamin E Levels

In this study of patients with type 2 diabetes, blood levels of two vital nutrients - glutathione and vitamin E - were found to increase when glucose levels dropped and blood sugar became better controlled.

In addition, levels of both of these nutrients increased even further in patients who received four weeks of vitamin E supplementation.

Although most people know about vitamin E, glutathione is not quite so well-known. It is a peptide consisting of glutamic acid, cysteine, and glycine. It serves as a critical co-enzyme for many reactions in the body.

In addition to the increased glutathione and vitamin E levels, levels of malonaldehyde, a naturally occurring possible carcinogen, were reduced following the reduction of blood glucose levels. Malonaldehyde occurs as a natural metabolic byproduct of prostaglandin synthesis and as an end product of polyunsaturated lipid peroxidation. The CDC has reported that there was clear evidence of carcinogenic activity in rats administered malonaldehyde, particularly effecting the thyroid gland and pancreas.

Annals of Nutrition and Metabolism 2000; 44: 11-13

COMMENT: Glutathione is one of the most essential antioxidants. One can take supplements for it, but the only form that works is the reduced form and this is very difficult to absorb orally. It is much more cost effective to supplement with precursors or items like alpha lipoic acid that regenerates glutathione. It also has the ability to regenerate other antioxidants such as vitamins C and E. Red meat and organ meats are the best sources of alpha lipoic acid. Glutamine is also a useful nutrient that improves intestinal health and also serves as a direct precursor to glutathione, and some investigators believe it to be the rate-limiting nutrient for glutathione formation.

Some nutritional authorities recommend taking a form of cysteine known as N-acetyl-cysteine (NAC), but I would advise against using this supplement if you still have mercury amalgam fillings because it could interfere with the detoxification of the mercury. Personally I consume 300 mg of alpha lipoic acid and 5,000 mg of glutamine and 2,500 mg of vitamin C before I do my seven-mile run as I believe it will maximize the glutathione production to decrease the damage from the free radicals that I generate when I exercise. Controlling the damage from free radicals is one of the keys to slowing down the aging process.