Long-term effects of the subtoxic coadministration of 3-nitropropionic acid and quinolinic acid in the rat striatum
Keywords:
Quinolinic acid, 3-nitropropionic acid, excitotoxicity, subtoxic, striatumAbstract
Introduction: Excitotoxicity and impaired energy metabolism are two events involved in
the neuronal damage observed in neurodegenerative diseases. 3-nitropropionic acid and
quinolinic acid are two toxins widely used to reproduce mechanisms of energy metabolism
dysfunction and excitotoxicity, respectively; however, it is unknown whether the co-admin-
istration of quinolinic acid and 3NP at subtoxic dose may have additive effects on long-term.
Objective: To determine the long-term effects of 3-nitropropionic acid and quinolinic acid
subtoxic administration on lipid peroxidation levels, mitochondrial functionality, total striatal
gamma-aminobutyric acid levels and cell morphology of the striatum neurons in rats. Meth-
ods: Male Wistar rats (260-300 g) were used and four groups were formed (n = 7-8; 3-4
rats for biochemical test and 4 rats for morphological analysis): 1) Control: 1 μL intrastriatal
(ie) saline and 0.5 mL intraperitoneally (ip) saline solution administration; 2) subtoxic 3-NP
(9 mg/kg) ip; 3) Subtoxic quinolinic acid (120 nM/μL) ie; and 4) subtoxic 3NP + subtoxic
quinolinic acid. After thirty days after the peroxidation levels and mitochondrial functionality
(both in striatal synaptosomes), striatal cell morphology, and total striatal gamma aminobutyric
acid levels were evaluated. Results: In the subtoxic co-administration group there was a
significant increase in peroxidation levels and in the number of striatal damaged cells, and
also a significant decrease of mitochondrial functionality with respect to subtoxic and control
groups. Moreover, the total striatal gamma aminobutyric acid content showed a decrease in
the subtoxic co-administration group relative to the control but this reduction was not signifi-
cant.
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