GSH and Arthritis

1: Indian J Med Sci. 2007 Jan;61(1):9-14.

Status of lipid peroxidation, glutathione, ascorbic acid, vitamin E and antioxidant enzymes in patients with osteoarthritis.


Surapaneni KM, Venkataramana G.

Department of Biochemistry, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Chinoutpally, Gannavaram, AP, India.

BACKGROUND: The exact pro-oxidant and antioxidant status in osteoarthritis patients is still not clear. To add a new insight to the question, changes in the erythrocyte lipid peroxidation products (MDA), levels of glutathione (GSH), ascorbic acid and plasma vitamin E (nonenzymatic antioxidant parameters); and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase in erythrocytes and plasma glutathione - S - transferase (GST) were measured in patients with osteoarthritis. AIM: This work was undertaken to assess oxidative stress and antioxidant status in patients with osteoarthritis. SETTINGS AND DESIGN: The study was conducted in 20 patients and compared to controls. Levels of erythrocyte MDA, GSH, ascorbic acid, plasma vitamin E; and activities of antioxidant enzymes were measured in patients with osteoarthritis. MATERIALS AND METHODS: Erythrocyte GSH was measured by the method of Beutler et al. Ascorbic acid levels were measured by the method of Tietz. Plasma vitamin E levels were measured by the method of Baker et al. MDA was determined as the measure of thio barbituric acid reactive substances (TBARS). SOD activity in the hemolysate was measured by the method of Misra and Fridovich. Activity of catalase was measured by the method of Beers and Sizer. GPX activity was measured as described by Paglia and Valentine in erythrocytes and Plasma GST activity was measured as described by Warholm et al. These parameters were measured in 20 patients and compared to controls. STATISTICAL ANALYSIS: Statistical analysis between group 1 (controls) and group 2 (patients) was performed by the student's t - test using the stat -view package. RESULTS: It was observed that there was a significant increase in erythrocyte MDA levels; SOD, GPX and plasma GST activities; and a significant decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalase activity in patients with osteoarthritis when compared to controls. CONCLUSIONS: The results of our study suggest higher oxygen-free radical production, evidenced by increased MDA and decreased GSH, ascorbic acid, vitamin E and catalase activity, support to the oxidative stress in osteoarthritis. The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress.

PMID: 17197733 [PubMed - indexed for MEDLINE]

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Clin Exp Rheumatol. 2002 Nov-Dec;20(6):761-6.

Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis.

Bazzichi L, Ciompi ML, Betti L, Rossi A, Melchiorre D, Fiorini M, Giannaccini G, Lucacchini A.

Rheumatic Diseases Unit, Medica Santa Chiara Hospital, University of Pisa, Pisa, Italy.

OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.

PMID: 12508766 [PubMed - indexed for MEDLINE]


J Appl Toxicol. 2001 Jan-Feb;21(1):69-73.

The glutathione defense system in the pathogenesis of rheumatoid arthritis.

Hassan MQ, Hadi RA, Al-Rawi ZS, Padron VA, Stohs SJ.

Faculty of Pharmacy & Medical Sciences, Amman University, Amman 19328, Jordan.

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA. Copyright 2001 John Wiley & Sons, Ltd.

PMID: 11180282 [PubMed - indexed for MEDLINE]


Arthritis Rheum. 2003 Dec;48(12):3419-30.

Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels.

Carlo MD Jr, Loeser RF.

Rush Medical College of Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.

OBJECTIVE: To examine the role of oxidative stress in mediating cell death in chondrocytes isolated from the articular cartilage of young and old adult human tissue donors. METHODS: Cell death induced by the oxidant SIN-1 was evaluated in the alginate bead culture system using fluorescent probes to assess membrane integrity. Generation of peroxynitrite by the decomposition of SIN-1 was confirmed by positive immunostaining of treated cells for 3-nitrotyrosine. Determinations of oxidized glutathione (GSSG) and reduced glutathione (GSH) were performed in monolayer cultures using an enzyme- recycling assay. Cells were depleted of intracellular glutathione either by the addition of DL-buthionine-(S,R)-sulfoximine or by removal of L-cystine from the culture media. The activity of cellular antioxidant enzymes was determined spectrophotometrically by the decay of substrate from the reaction mixture. RESULTS: More chondrocytes (>2-fold) from old donors (>/=50 years) died after exposure to 1 mM SIN-1 relative to those derived from young donors (18-49 years). Although autocrine production of insulin-like growth factor 1 (IGF-1) promotes chondrocyte survival, pretreatment with IGF-1 could not prevent the cell death induced by SIN-1 exposure. Cells isolated from old donors had a higher ratio of GSSG to GSH. Glutathione reductase is the principal enzyme involved in the regeneration of GSH from GSSG. Treatment of chondrocytes with SIN-1 to induce oxidative stress in vitro resulted in the decreased activity of glutathione reductase and thioredoxin reductase, but not catalase. Cells depleted of intracellular glutathione were more susceptible to cell death induced by SIN-1. CONCLUSION: These results provide evidence that increased oxidative stress with aging makes chondrocytes more susceptible to oxidant-mediated cell death through the dysregulation of the glutathione antioxidant system. This may represent an important contributing factor to the development of osteoarthritis in older adults.

PMID: 14673993 [PubMed - indexed for MEDLINE]


1: Indian J Med Res. 2003 Oct;118:178-81.


Antioxidant status & lipid peroxidation in patients with rheumatoid arthritis.

Karatas F, Ozates I, Canatan H, Halifeoglu I, Karatepe M, Colakt R.

Department of Chemistry, College of Science, Firat University, Elazig 23119, Turkey.

BACKGROUND & OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating, chronic multisystem disease with an unknown etiology. Recent findings indicate that increased oxidative stress and/or defective antioxidant status contribute to the etiology of RA. The present study was undertaken to examine the oxidant and antioxidant systems in patients with RA and healthy controls. METHODS: Twenty two patients with RA and 20 healthy volunteers were included in the study. Levels of malondialdehyde (MDA) and antioxidant vitamins (A, E, C) in serum samples were determined by high performance liquid chromatography (HPLC). Spectrophotometric methods were used to determine activity levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), in erythrocytes. RESULTS: MDA levels in patients with RA were found to be significantly (P<0.005) higher than controls whereas levels of vitamins A, E, C and activities of GSH-Px, SOD were lower in the patients compared to controls (P<0.005 for SOD and antioxidant vitamins; P<0.05 for GSH-Px). INTERPRETATION & CONCLUSION: There was an increased oxidative stress and a low antioxidant status in patients with RA. These changes are probably due to efforts for reducing lipid peroxidation and hence to lower tissue damage.

: Cell Biochem Funct. 2004 Jan-Feb;22(1):53-7.


Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis.

Kamanli A, Naziroglu M, Aydilek N, Hacievliyagil C.

Department of Physical Medicine and Rehabilitation, Medical Faculty, Firat University, Elazig, Turkey.

In recent years, a great number of studies have investigated the possible role of reactive oxygen species in the aetiology and pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate plasma concentrations of vitamin E, beta-carotene, activities of glutathione peroxidase (GSH-Px) and catalase, levels of lipid peroxidation (MDA) and reduced glutathione (GSH) in 36 patients with rheumatoid arthritis (RA) and 22 healthy age-matched controls. The plasma activity of GSH-Px and catalase (p < 0.001), levels of GSH (p < 0.01), concentration of beta-carotene (p < 0.05) and vitamin E (p < 0.001), haemoglobin and hematocrit (p < 0.05) were significantly lower in patients with RA than in controls. The MDA levels (p < 0.01), C reactive protein, rheumatoid factor, anti-streptolysin-o values (p < 0.001), platelet count (p < 0.05) and erythrocyte sedimentation rate (p < 0.001) were higher in the patient group than in the control group. These results provide some evidence for a potential role of increased lipid peroxidation and decreased enzymic and non-enzymic antioxidants in RA by its inflammatory character. These results suggested that oxidant stress plays a very important role in the pathogenesis of RA. Copyright 2003 John Wiley & Sons, Ltd.