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.
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.
Lorenc-Koci
Elzbieta
E
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12, Smetna Street, PL-31-343 Kraków, Poland. lorenc@if-pan.krakow.pl
Sokołowska
Maria
M
Kwiecień
Inga
I
Włodek
Lidia
L
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D026403:S-Nitrosothiols; D044005:Tetrahydroisoquinolines; D009569:Nitric Oxide; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D004298:Dopamine