Role of serotonin in cerebral oxidative stress in rats.
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter synthesized by the aromatic amino acid decarboxylase using 5-hydroxytryptophan (5-HTP) as a substrate. It was recently shown that serotonin and its precursor have powerful antioxidant properties. The aim of this study was to evaluate the effect of reduction in 5-HT levels by parachlorophenylalanine (pCPA) and their restoration by 5-HTP administration on lipid peroxidation and antioxidant status in rat brain. Serotonin levels were decreased by p-chlorophenylalanine administration. The effect of p-chlorophenylalanine was counteracted by the intraperitoneal administration of 5-hydroxytryptophan. We evaluated the concentration of serotonin, malonyl dialdehyde and the status of antioxidants (GSH, catalase and superoxide dismutase) in brain. The results showed that p-chlorophenylalanine (300 mg/kg) induced a depletion of serotonin concentration and antioxidant status, as well as enhancing malonyl dialdehyde concentration in brain. The exogenous administration of 5-hydroxytryptophan prevented all effects induced by p-chlorophenylalanine in brain tissue. The recovery of the neurotransmitter concentration in brain was related to the reduction of lipid peroxide generation and improved antioxidant status. In conclusion, our study supports the view that the antioxidant properties of serotonin protect against basal oxidative stress in brain.
Muñoz-Castañeda
Juan R
JR
Department of Biochemistry and Molecular Biology, School of Medicine, Avda Menendez Pidal s/n 14004 Córdoba, Spain. juanr.munoz.exts@juntadeandalucia.es.
Montilla
Pedro
P
Padillo
Francisco J
FJ
Bujalance
Inmaculada
I
Muñoz
Maria C
MC
Muntané
Jordi
J
Túnez
Isaac
I
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D008054:Lipid Peroxides; D012702:Serotonin Antagonists; D012701:Serotonin; D006916:5-Hydroxytryptophan; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D010134:Fenclonine