Glutathione in Health and Disease: Pharmacotherapeutic Issues

Lomaestro, Ben M.; Malone, Margaret

doi:10.1177/106002809502901213

Cited by 194 publications

(128 citation statements)

References 72 publications

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“…Other studies have shown that PDT, via NF-kB, induced the up-regulation of γ-glutamylcysteine synthetase expression in response to oxidative stress-induced GSH depletion (30). Furthermore, discrepancies have been noted concerning the relationship that exists between antioxidant levels and tumor damage, as GSH levels have been reported to be increased, decreased or unaltered following PDT (31). Additionally, it has been shown that the activation of apoptosis-executing caspases actually requires sustained glutathione levels as these proteases possess an essential cysteine thiol in the active site (29).…”

Section: Discussionmentioning

confidence: 94%

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Filip

Clichici

Daicoviciu

et al. 2011

Braz J Med Biol Res

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Section: Discussionmentioning

confidence: 94%

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Filip

Clichici

Daicoviciu

et al. 2011

Braz J Med Biol Res

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“…In fact, erythropoietin might have been responsible for aggravating the photosensitivity in our patient. Glutathione deficiency resulting from sun exposure and oxidative stress might also be responsible for the development of pseudoporphyria (6). N-acetyl cysteine increases the intracellular glutathione biosynthesis in this setting (7), and its long-term use is beneficial in the treatment of pseudoporphyria.…”

Section: Discussionmentioning

confidence: 99%

Pseudoporphyria in a Peritoneal Dialysis Patient

2015

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“…Glutathione peroxidase, reductase, transferase(s) and glutaredoxin all utilize GSH in reactions that remove peroxide, as well as potential endogenous and exogenous toxins, control the redox state of the cell and regulate protein function through thiolation and dethiolation. This network of enzymes using GSH as substrate have been implicated in DNA synthesis and repair, protein synthesis, amino acid transport, and enzyme activation or inactivation (Lomaestro & Malone 1995). GSH may also act as a redox modifier of some ionotropic currents (Ogita et al 1995).…”

Section: Abstract Oxidative Stress; Glutathione Ethyl Ester; Neurodegmentioning

confidence: 99%

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: Relevance to Parkinson's disease

Zeevalk

Manzino

Sonsalla

et al. 2007

Experimental Neurology

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Parkinson's disease (PD) is associated with loss of total glutathione (GSH) which may contribute to progressive cell death. Peripheral GSH administration has been used clinically with reported benefits. Despite this, there is little specific information to characterize its cellular uptake or clearance, brain elevation with peripheral delivery or neuroprotective efficacy in PD models. The current study was carried out to provide this information using in vitro and in vivo approaches. In rat mesencephalic culture, the monoethyl-ester of GSH (GEE), but not GSH (1-10mM, 24hr) produced a dosedependent elevation in GSH. The half-life for clearance was 10.14hr and was not different in cells depleted of GSH prior to loading. Elevation of GSH with GEE protected neurons from oxidative stress with H 2 O 2 or metabolic stress with the complex I and II inhibitors, MPP + and malonate, respectively. To determine if peripheral administration of GEE could elevate brain GSH levels, rats were administered 0.1-50mg/kg/d GEE via osmotic minipump either subcutaneously (sc) or via a cannula placed into the left cerebral ventricle (icv) for 28d. Only central delivery of GEE resulted in significant elevations of brain GSH. Elevation of brain GSH by icv infusion of GEE was examined for its neuroprotective effects against chronic central delivery of MPP + . Infusion of 0.142mg/kg/d MPP + for 28d caused a selective ipsilateral loss of striatal dopamine. Co-infusion of MPP + with 10mg/kg/d GEE significantly protected against striatal dopamine loss. These findings show that the ethyl ester of GSH but not GSH per se can elevate intracellular GSH, that brain elevation of GSH requires central delivery of the ethyl-ester and that this elevation provides neuroprotection against oxidative stress or chronic mitochondrial impairment. Keywords oxidative stress; glutathione ethyl ester; neurodegeneration; neuroprotectionThe underlying etiology of sporadic Parkinson's disease (PD) remains elusive, although much evidence implicates oxidative stress in the process. The substantia nigra (SN) from autopsied brain material has been shown to contain increased levels of protein carbonyls (Alam et al. 1997), malondialdehyde or 4-hydroxynonenol (Dexter et al. 1994a;Yoritaka et al. 1996) and 8-hydroxy-2-deoxyguanosine (Sanchez-Ramos et al. 1994), indicative of oxidative damage to proteins, lipids and DNA, respectively. One of the earliest biochemical derangements observed in the SN of patients with PD is loss of total glutathione levels (Perry & Yong 1986; Corresponding Author: Gail D. Zeevalk, zeevalgd@umdnj.edu, Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Building UBHC, Rm 405D, 675, Hoes Lane, Piscataway, N.J. 08854, Phone: 732 235-3494, Fax: 732 235-5295 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting p...

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Glutathione in Health and Disease: Pharmacotherapeutic Issues

Abstract: The list of potential indications for modulation of GSH is extensive and broad. This review introduces clinicians to what GSH is, its basic chemistry, and some areas of active research.

Cited by 194 publications

References 72 publications

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Pseudoporphyria in a Peritoneal Dialysis Patient

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: Relevance to Parkinson's disease

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