Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem of the rat

Pharmacol Biochem Behav. 1996 Jun;54(2):377-83. doi: 10.1016/0091-3057(95)02161-2.

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), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) 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 brain stem of 3-month-old male Wistar rats given allopurinol (300 mg/kg day by gavage) for 3 days before a single MPTP 35 mg/kg dose IP. Allopurinol alone decreased uric acid and increased xanthine levels both in the striatum and in the brain stem; moreover, allopurinol decreased striatal DOPAC + HVA/DA ratio and increased 5-HIAA/5HT ratio in the brainstem. Allopurinol affected neither regional MPTP nor MPP+ disposition. Allopurinol potentiated the MPTP-induced decrease in the DOPAC+HVA/DA ratio and increase in striatal AA oxidation; in addition, allopurinol antagonised the MPTP-induced: (i) increase in uric acid levels; (ii) decrease in NA levels in both regions, in DA levels, and in the 5-HIAA/5-HT ratio in the brain stem: (iii) increase in AA oxidation in the brain stem. In conclusion, the MPP(+)-induced oxidative stress mediated by xanthine oxidase seems to be involved in DA depletion in the brainstem and in NA depletion in both regions; moreover, striatal uric acid may have an active role in the neuronal antioxidant pool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Allopurinol / pharmacology*
  • Animals
  • Antimetabolites / pharmacology*
  • Ascorbic Acid / metabolism
  • Brain Stem / drug effects
  • Brain Stem / metabolism*
  • Catecholamines / metabolism
  • Dopamine Agents / pharmacology*
  • Hypoxanthine / metabolism
  • Male
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Oxidative Stress / drug effects*
  • Purines / metabolism
  • Rats
  • Rats, Wistar
  • Xanthines / metabolism

Substances

  • Antimetabolites
  • Catecholamines
  • Dopamine Agents
  • Purines
  • Xanthines
  • Hypoxanthine
  • Allopurinol
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Ascorbic Acid