Publications (6)2.11 Total impact
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Article: Effects of allopurinol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurochemical changes in the striatum and in the brainstem of the rat
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ABSTRACT: Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid (DHAA), glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats, given allopurinol (500 mg/kg day by gavage) for 3 days before a single MPTP 52 mg/kg dose i.p. Allopurinol alone decreased uric acid and hypoxanthine levels in the striatum and in the brainstem; moreover, allopurinol increased AA oxidation and decreased striatal DA metabolites. Allopurinol affected neither regional MPTP and MPP+ levels nor the MPTP-induced inhibition of striatal DA oxidative metabolism. On the contrary, the MPTP-induced increase in uric acid levels and decrease in xanthine, hypoxanthine and NA levels were fully antagonised. Such findings demonstrate that the claimed MPP(+)-induced oxidative stress mediated by xanthine oxidase may be involved at least in the NA depletion; moreover, uric acid may have a physiological role as an active component of the neuronal antioxidant pool.Neuroscience Letters 02/1995; · 2.11 Impact Factor -
Article: Investigations into the relationship between the dopaminergic system and ascorbic acid in rat striatum
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ABSTRACT: Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) were determined by HPLC in the striatum of male Wistar rats after single or repeated injections of apomorphine (1 mg/kg/day s.c.) and/or haloperidol (1 mg/kg/day i.p.), and 24 h after the last drug administration. Apomorphine significantly reduced the DOPAC/DA ratio and increased the DHAA/AA ratio; these ratio changes were significantly correlated ( r = −0.9969, P < 0.0005). Haloperidol greatly increased the DOPAC/DA ratio; the DHAA/AA ratio was also slightly increased, but there was no significant correlation. When apomorphine was associated with haloperidol, the resulting DOPAC/DA ratio was significantly lower than after haloperidol alone; the DHAA/AA ratio was also significantly reduced in contrast to the effect of apomorphine alone. It is concluded that a non-selective DA receptor activation mediates, in a correlated way, both the inhibition of DA turnover and the increase of AA oxidation in the rat striatum. -
Article: The Effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat
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ABSTRACT: Dopamine (DA). 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels were determined by HPLC in the striatal synaptosomal fraction and in the whole striatum of rats, whose fronto-parietal cortex had been bilaterally ablated, after a single injection of d-amphetamine (2.0 mg/kg i.p.). d-Amphetamine significantly increased the DHAA/AA ratio in unoperated and sham-operated rats, but failed to increase it in ablated rats, as compared to pertinent saline-treated groups. In the synaptosomal fraction, d-amphetamine significantly decreased the DHAA/AA ratio in unoperated, sham-operated and ablated rats. d-Amphetamine significantly decreased the DOPAC/DA ratio in the whole striatum and significantly increased it in the striatal synaptosomal fraction in all experimental groups. Cortical ablation greatly increased d-amphetamine-induced motor hyperactivity. We conclude that the d-amphetamine-induced increase in AA striatal oxidation requires integrity of the cortico-striatal glutamatergic pathways. Further, AA oxidation occurs in the extracellular space. The cortico-striatal glutamatergic pathways exert an inhibitory modulation on d-amphetamine behavioral effects. -
Article: Effect of morphine on striatal dopamine metabolism and ascorbic and uric acid release in freely moving rats
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ABSTRACT: Recent ex vivo findings have shown that morphine increases dopamine (DA) and xanthine oxidative metabolism and ascorbic acid (AA) oxidation in the rat striatum. In the present study, we evaluated the effects of subcutaneous daily morphine (20 mg/kg) administration on DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), AA and uric acid in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection. On the first day, morphine administration caused a significant increase in extracellular DA, DOPAC, HVA, AA and uric acid concentrations over a 3 h period after morphine. In all treated rats (n = 7), individual concentrations of DOPAC + HVA were directly correlated with individual AA and uric acid concentrations. Last morphine administration on the 4th day increased DOPAC, HVA, AA and uric acid concentrations but failed to increase those of DA. Individual DOPAC + HVA concentrations were still directly correlated with individual AA and uric acid concentrations. These results suggest that systemic morphine increases both striatal DA release and DA and xanthine oxidative metabolism. Only the former effect undergoes tolerance. The increase in DA oxidative metabolism is highly correlated with that of xanthine. The subsequent enhancement in reactive oxygen species production may account for the increase in extracellular AA. -
Article: Effects of ageing on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxic effects on striatum and brainstem in the rat
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ABSTRACT: In 3- and 18-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), noradrenaline (NA), uric acid, glutathione (GSH) and 1-methyl-4-phenylpyridinium ion (MPP<sup>+</sup>) were determined by HPLC in the striatum and/or in the brainstem 24 h after single injections of MPTP (12–35 mg/kg i.p.). Aged rats had lower baseline levels of AA and GSH, compared to young rats. In aged rats, MPTP 35 mg/kg induced a 70% death rate and a decrease in striatal DOPAC/DA ratio which was correlated to MPP<sup>+</sup> concentrations ( r = −0.840, P < 0.005); in addition, MPTP did not increase AA oxidation. In the brainstem, the MPTP-induced decrease in NA levels and increase in uric acid levels were significantly correlated to the MPP<sup>+</sup> concentrations ( r = −0.709, P < 0.05, and r = +0.888, P < 0.001, respectively). In conclusion, evidence is given of a mechanism of toxicity of MPTP involving oxidative stress produced by xanthine oxidase; in addition, in aged rats the neuronal antioxidant system (levels of AA and GSH) is considerably lower than in young rats and may play an enabling role in the MPTP age-related neurotoxic effects on striatum and brainstem. -
Article: Further ivestigations into the relationship between the dopanminergic system ascorbic acid and uric acid in the rat striatum
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ABSTRACT: Levels of dopaminc (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), and uric acid were determined in the rat striatum following single apomorphine (1 mg/kg), scopolamine (0.6 mg/kg), pilocarpine (4 mg/kg), or pilocarpine + scopolamine (4 and 0.6 mg/kg, respectively) injections. The decrease in DOPAC levels and in the DOPAC/DA ratio, induced by the pharmacological manipulation, was linearly correlated with the increase in DHAA levels (r = −0.9060, P < 0.05) and with the increase in the DHAA / AA ratio (r = −0.9004, P < 0.05), respectively. I dopaminergic activaction or cholinergic inhibition both increase striatal AA oxidation, which is correlated with a decrease in DA turnover.
