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Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide, S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl transpeptidase in the dopaminergic structures of rat brain.
Brain Res. 2005 Jul 12; 1049(2):133-46.BR

Abstract

Depletion of glutathione (GSH), nitrosative stress and chronic intoxication with some neurotoxins have been postulated to play a major role in the pathogenesis of Parkinson's disease. This study aimed to examine the effects of acute and chronic treatments with 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo-/exogenous substance suspected of producing Parkinsonism in human, on the levels of nitric oxide (NO), S-nitrosothiols and glutathione (GSH) in the whole rat brain and in its dopaminergic structures. TIQ administered at a dose of 50 mg/kg i.p. significantly increased the tissue concentrations of NO and GSH in the substantia nigra (SN), striatum (STR) and cortex (CTX) of rats receiving this compound both acutely and chronically. Moreover, it decreased the level of oxidized glutathione (GSSG) and enhanced GSH:GSSG ratio affecting in this way the redox state of brain cells. TIQ also increased the level of S-nitrosothiols when measured in the whole rat brain and CTX, although it markedly decreased their level in the STR after both treatments. Inhibition of the constitutive NO synthase by l-NAME in the presence of TIQ caused decreases in GSH and S-nitrosothiol levels in the brain. The latter effect shows that the TIQ-mediated increases in GSH and S-nitrosothiol concentrations were dependent on the enhanced NO level. The above-described results suggest that TIQ can act as a modulator of GSH, NO and S-nitrosothiol levels but not as a parkinsonism-inducing agent in the rat brain.

Authors+Show Affiliations

Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12, Smetna Street, PL-31-343 Kraków, Poland. lorenc@if-pan.krakow.plNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15946655

Citation

Lorenc-Koci, Elzbieta, et al. "Treatment With 1,2,3,4-tetrahydroisoquinolone Affects the Levels of Nitric Oxide, S-nitrosothiols, Glutathione and the Enzymatic Activity of Gamma-glutamyl Transpeptidase in the Dopaminergic Structures of Rat Brain." Brain Research, vol. 1049, no. 2, 2005, pp. 133-46.
Lorenc-Koci E, Sokołowska M, Kwiecień I, et al. Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide, S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl transpeptidase in the dopaminergic structures of rat brain. Brain Res. 2005;1049(2):133-46.
Lorenc-Koci, E., Sokołowska, M., Kwiecień, I., & Włodek, L. (2005). Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide, S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl transpeptidase in the dopaminergic structures of rat brain. Brain Research, 1049(2), 133-46.
Lorenc-Koci E, et al. Treatment With 1,2,3,4-tetrahydroisoquinolone Affects the Levels of Nitric Oxide, S-nitrosothiols, Glutathione and the Enzymatic Activity of Gamma-glutamyl Transpeptidase in the Dopaminergic Structures of Rat Brain. Brain Res. 2005 Jul 12;1049(2):133-46. PubMed PMID: 15946655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide, S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl transpeptidase in the dopaminergic structures of rat brain. AU - Lorenc-Koci,Elzbieta, AU - Sokołowska,Maria, AU - Kwiecień,Inga, AU - Włodek,Lidia, PY - 2004/12/14/received PY - 2005/04/14/revised PY - 2005/04/15/accepted PY - 2005/6/11/pubmed PY - 2005/10/20/medline PY - 2005/6/11/entrez SP - 133 EP - 46 JF - Brain research JO - Brain Res VL - 1049 IS - 2 N2 - Depletion of glutathione (GSH), nitrosative stress and chronic intoxication with some neurotoxins have been postulated to play a major role in the pathogenesis of Parkinson's disease. This study aimed to examine the effects of acute and chronic treatments with 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo-/exogenous substance suspected of producing Parkinsonism in human, on the levels of nitric oxide (NO), S-nitrosothiols and glutathione (GSH) in the whole rat brain and in its dopaminergic structures. TIQ administered at a dose of 50 mg/kg i.p. significantly increased the tissue concentrations of NO and GSH in the substantia nigra (SN), striatum (STR) and cortex (CTX) of rats receiving this compound both acutely and chronically. Moreover, it decreased the level of oxidized glutathione (GSSG) and enhanced GSH:GSSG ratio affecting in this way the redox state of brain cells. TIQ also increased the level of S-nitrosothiols when measured in the whole rat brain and CTX, although it markedly decreased their level in the STR after both treatments. Inhibition of the constitutive NO synthase by l-NAME in the presence of TIQ caused decreases in GSH and S-nitrosothiol levels in the brain. The latter effect shows that the TIQ-mediated increases in GSH and S-nitrosothiol concentrations were dependent on the enhanced NO level. The above-described results suggest that TIQ can act as a modulator of GSH, NO and S-nitrosothiol levels but not as a parkinsonism-inducing agent in the rat brain. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15946655/Treatment_with_1234_tetrahydroisoquinolone_affects_the_levels_of_nitric_oxide_S_nitrosothiols_glutathione_and_the_enzymatic_activity_of_gamma_glutamyl_transpeptidase_in_the_dopaminergic_structures_of_rat_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(05)00602-5 DB - PRIME DP - Unbound Medicine ER -