Selective Modification of Glutathione Metabolism

Meister, Alton

doi:10.1126/science.6836290

Cited by 1,172 publications

(582 citation statements)

References 43 publications

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“…GSH is a tripeptide containing cysteine and AFB 1 easily conjugates with GSH (Janssen et al 1993). GSH is also a major component of red blood cells that plays a central role in the antioxidant defenses of cells (Meister 1983;Ray 1984). Whereas, the significant decrease in the levels of GSH observed in erythrocytes after AFB 1 exposure causes decreased degradation of lipid peroxides leading to their accumulation thus amplifying the toxicity of AFB 1 .…”

Section: Discussionmentioning

confidence: 99%

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

Türkez

Geyikoğlu

2010

Cytotechnology

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Aflatoxin B 1 is the most potent pulmonary and hepatic carcinogen. Since the eradication of Aflatoxin B 1 contamination in agricultural products has been difficult, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boric acid is the major component of industry and its antioxidant role has recently been reported. The present study assessed, for the first time, the effectiveness of boric acid following exposure to Aflatoxin B 1 on human whole blood cultures. The biochemical characterizations of glutathione and some enzymes have been carried out in erythrocytes. Alterations in malondialdehyde level were determined as an index of oxidative stress. The sister-chromatid exchange and micronucleus tests were performed to assess DNA damages in lymphocytes. Aflatoxin B 1 treatment significantly reduced the activities of antioxidants by increasing malondialdehyde level (30.53 and 51.43%) of blood, whereas, the boric acid led to an increased resistance of DNA to oxidative damage induced by Aflatoxin B 1 in comparison with control values (P \ 0.05). In conclusion, the support of boric acid was especially useful in Aflatoxin-toxicated blood. Thus the risk on tissue targeting of Aflatoxin B 1 could be reduced ensuring early recovery from its toxicity.

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Section: Discussionmentioning

confidence: 99%

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

Türkez

Geyikoğlu

2010

Cytotechnology

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“…It has been demonstrated that CDDP induced nephrotoxicity can be presented by GSH in renal tissues (Anderson et al, 1990). Furthermore, it has been reported that GSH reacts with ROS and plays a role in the reduction of hydrogen peroxide and organic peroxides (Meister, 1983;Martensson, 1991) and that CDDP is inactivated by direct binding to GSH (Meijer et al, 1990). Ishikawa et al (1993) showed that CDDP reacts with intracellular GSH and that the resulting glutathione-platinum complex is actively exported from leukaemia cells via a GS-X pump.…”

Section: Measurement Of Intracellular Ros Generationmentioning

confidence: 99%

Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells

Miyajima

Nakashima²,

Yoshioka³

et al. 1997

Br J Cancer

162

101

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Summary This study was undertaken to investigate the intracellular induction of reactive oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and diethylmaleate (DEM). CDDP-induced cytotoxicity in KU7 cells and its modulation by GSH depletors were determined using spectrophotometric measurement with crystal violet staining. The effects of GSH depletors on intracellular GSH levels were confirmed using the GSH reductase-DTNB recycling method. Intracellular ROS generation induced by CDDP with or without GSH depletors was estimated from the amount of intracellular dichlorofluorescein (DCF), an oxidized product of dichlorofluorescein (DCFH), which was measured with an anchored cell analysis and sorting system. The cytotoxic effects of CDDP (IC50 15.0 ± 2.5 gIM) were significantly enhanced by BSO (IC50 9.3 ± 2.6 gM, P < 0.01) and DEM (IC50 10.3 ± 0.3 gM, P < 0.01). BSO and DEM produced a significant depletion in intracellular GSH levels (9.6 ± 0.4 nmol 10-6 cells, 17.9 ± 1.0 nmol 10-6 cells) compared with the controls (30.5 ± 0.6 nmol 10-6 cells). Intracellular DCF production in KU7 cells treated with CDDP (1.35 ± 0.33 g1M) was significantly enhanced by the addition of BSO (4.43 ± 0.33 gM) or DEM (3.12 ± 0.22 gM) at 150 min. These results suggest that ROS may play a substantial role in CDDPinduced cytotoxicity and that GSH depletors augment its cytotoxicity through an enhancement of ROS generation in bladder cancer cells.

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“…Reduced glutathione plays an important role in the protection of cells and tissue structures (23). Its role includes detoxication of xenobiotics, free radicals, peroxides and regulation of immune function.…”

Section: Discussionmentioning

confidence: 99%

Effect of type II collagen treatment on the antioxidant status in immune tissues of adjuvant induced arthritic rats

Ganesan

Hariprasad

Chandrasekaran

2003

Indian J Clin Biochem

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Adjuvant induced arthritis (AIA) is a model widely used to study Rheumatoid arthritis (RA). In the present study, lipid peroxides level in spleen and thymus of AIA rats was observed to be significantly high compared to normal rats. A significant decrease in ascorbic acid (ASA), reduced glutathione (GSH), superoxide dismutase activity (SOD) was also observed in spleen and thymus of AIA rats compared to normal rats. There was also a steady increase in the circulating immune complex level (CIC) throughout the experimental period in serum of AIA rats. In the present investigation, it was decided to study the effect of pre and post treatment with TYPE II collagen on the antioxidant status and the circulating immune complex level in AIA rats. The results from the present work indicates that the pretreatment with TYPE II collagen was effective in bringing significant changes on all the parameters studied in AIA rats. The post treatment with TYPE II collagen was effective in bringing significant changes on the CIC immune complex level and GSH content in the thymus tissue of AIA rats. The present work suggests that the pre treatment with TYPE II collagen was more effective in suppressing the disease than the post treatment.

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Selective Modification of Glutathione Metabolism

Cited by 1,172 publications

References 43 publications

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells

Effect of type II collagen treatment on the antioxidant status in immune tissues of adjuvant induced arthritic rats

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