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Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid.
Arch Toxicol. 2005 Mar; 79(3):140-6.AT

Abstract

The purpose of this study was to examine the effects of DL: -alpha-lipoic acid (LA) on arsenic (As) induced alteration of glutathione (GSH) level and of the activity of glutathione-related enzymes-glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH)-in rat brain regions (cortex, hypothalamus, striatum, cerebellum and hippocampus). Male Wistar rats of 150+/-10 g weight were divided into four groups: control and three experimental groups supplemented with arsenic (sodium arsenite) alone (100 ppm mixed in drinking water), lipoic acid alone (70 mg kg(-1) body weight), arsenic plus lipoic acid (100 ppm arsenic in drinking water plus 70 mg lipoic acid kg(-1) body weight). The arsenic content of brain regions was found to increase with the administration of sodium arsenite. Arsenic exposure elicited a significant decline in glutathione content and in the activity of related enzymes, with the greatest decreases seen in the cortex, striatum, and hippocampus, whereas there were no significant differences between control rats and the group treated with lipoic acid alone. Highly elevated content of the thiobarbituric acid-reactive substance malondialdehyde (MDA) in the brain regions of arsenic-exposed rats reflected extensive lipid peroxidation (LPO) processes. Simultaneous lipoic acid treatment was effective in reducing brain regional arsenic levels and lipid peroxidation and in increasing the glutathione content and the activity of its related enzymes. Lipoic acid, by acting as an alternative sulfhydryl nucleophile to glutathione, prevents its oxidation to glutathione disulfide in detoxifying reactions against reactive oxygen species and consequently increases the activity of glutathione-related enzymes.

Authors+Show Affiliations

Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, 600 113, Chennai, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15798887

Citation

Shila, Samuel, et al. "Arsenic Intoxication-induced Reduction of Glutathione Level and of the Activity of Related Enzymes in Rat Brain Regions: Reversal By DL-alpha-lipoic Acid." Archives of Toxicology, vol. 79, no. 3, 2005, pp. 140-6.
Shila S, Subathra M, Devi MA, et al. Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid. Arch Toxicol. 2005;79(3):140-6.
Shila, S., Subathra, M., Devi, M. A., & Panneerselvam, C. (2005). Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid. Archives of Toxicology, 79(3), 140-6.
Shila S, et al. Arsenic Intoxication-induced Reduction of Glutathione Level and of the Activity of Related Enzymes in Rat Brain Regions: Reversal By DL-alpha-lipoic Acid. Arch Toxicol. 2005;79(3):140-6. PubMed PMID: 15798887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid. AU - Shila,Samuel, AU - Subathra,Marimuthu, AU - Devi,Muthuswamy Anusuya, AU - Panneerselvam,Chinnakkannu, Y1 - 2004/11/11/ PY - 2004/06/14/received PY - 2004/08/25/accepted PY - 2005/3/31/pubmed PY - 2005/12/24/medline PY - 2005/3/31/entrez SP - 140 EP - 6 JF - Archives of toxicology JO - Arch Toxicol VL - 79 IS - 3 N2 - The purpose of this study was to examine the effects of DL: -alpha-lipoic acid (LA) on arsenic (As) induced alteration of glutathione (GSH) level and of the activity of glutathione-related enzymes-glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH)-in rat brain regions (cortex, hypothalamus, striatum, cerebellum and hippocampus). Male Wistar rats of 150+/-10 g weight were divided into four groups: control and three experimental groups supplemented with arsenic (sodium arsenite) alone (100 ppm mixed in drinking water), lipoic acid alone (70 mg kg(-1) body weight), arsenic plus lipoic acid (100 ppm arsenic in drinking water plus 70 mg lipoic acid kg(-1) body weight). The arsenic content of brain regions was found to increase with the administration of sodium arsenite. Arsenic exposure elicited a significant decline in glutathione content and in the activity of related enzymes, with the greatest decreases seen in the cortex, striatum, and hippocampus, whereas there were no significant differences between control rats and the group treated with lipoic acid alone. Highly elevated content of the thiobarbituric acid-reactive substance malondialdehyde (MDA) in the brain regions of arsenic-exposed rats reflected extensive lipid peroxidation (LPO) processes. Simultaneous lipoic acid treatment was effective in reducing brain regional arsenic levels and lipid peroxidation and in increasing the glutathione content and the activity of its related enzymes. Lipoic acid, by acting as an alternative sulfhydryl nucleophile to glutathione, prevents its oxidation to glutathione disulfide in detoxifying reactions against reactive oxygen species and consequently increases the activity of glutathione-related enzymes. SN - 0340-5761 UR - https://www.unboundmedicine.com/medline/citation/15798887/Arsenic_intoxication_induced_reduction_of_glutathione_level_and_of_the_activity_of_related_enzymes_in_rat_brain_regions:_reversal_by_DL_alpha_lipoic_acid_ L2 - https://doi.org/10.1007/s00204-004-0614-8 DB - PRIME DP - Unbound Medicine ER -