Effect of N-acetylcysteine on the spinal-cord glutathione system and nitric-oxide metabolites in rats with neuropathic pain.
Since N-acetylcysteine (NAC) is a donor of cysteine, we studied the relationship between NAC and concentration of oxidized and reduced glutathione (GSH/GSSG ratio), and glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve that received NAC (150mg/kg/day, i.p.) or 0.9% saline solution for 3 or 10 days. Hydrogen peroxide (H2O2) and nitric-oxide (NO) metabolites were also measured. Von Frey hair and hot-plate tests showed hyperalgesia at day 1 in CCI rats. Hyperalgesia persisted at all other times in saline-treated CCI rats, but returned to pre-injury values in NAC-treated CCI rats after 3 postoperative days. GST activity and the GSH/GSSG ratio increased in saline-treated CCI rats, while the NAC treatment increased GST and GPx activities at day 10, with no significant change in the GSH/GSSG ratio. NAC treatment did not affect H2O2 levels, but it reduced NO metabolites in CCI rats 3 days after the surgery. Thus, the anti-hyperalgesic effect of NAC appears not to involve its action as a cysteine precursor for GSH synthesis, but involves a decrease in NO.
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: deia.horst@gmail.com.
Andréa
A
Horst
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Carolina
C
Kolberg
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Maira S
MS
Moraes
Departamento de Farmacologia e Fisiologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Ana Paula K
AP
Riffel
Departamento de Farmacologia e Fisiologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Isabela A
IA
Finamor
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Adriane
A
Belló-Klein
Departamento de Farmacologia e Fisiologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Maria Amália
MA
Pavanato
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Wania A
WA
Partata
D000111:Acetylcysteine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003251:Constriction, Pathologic; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology; D008161:Lumbosacral Region; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D010812:Physical Stimulation; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014110:Touch
D000700:Analgesics; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D000111:Acetylcysteine
Chronic constriction; Glutathione peroxidase; Glutathione-S-transferase; Hydrogen peroxide; Oxidized and reduced glutathione; Sciatic nerve