Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat

Neurosci Lett. 1995 Jun 9;192(2):73-6. doi: 10.1016/0304-3940(95)11613-2.

Abstract

Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid, glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and and 3-methoxytyramine were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats given manganese (MnCl2, 200 mg/kg/day for 7 days by gavage) alone or associated with allopurinol. Allopurinol alone (300 mg/kg/day for 4 days by gavage) decreased uric acid and increased xanthine levels both in the striatum and in the brainstem; moreover, allopurinol decreased the striatal DOPAC + HVA/DA ratio. Allopurinol antagonised the Mn-induced: (a) increase in the DOPAC + HVA/DA ratio; (b) increase in uric acid levels and AA oxidation; and (c) decrease in GSH and NA levels. We conclude that allopurinol may protect against Mn-induced oxidative stress by inhibiting both DA oxidative metabolism and xanthine oxidase-mediated formation of reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology*
  • Animals
  • Brain Stem / drug effects
  • Brain Stem / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Male
  • Manganese / pharmacology*
  • Norepinephrine / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Uric Acid / metabolism
  • Xanthine
  • Xanthines / metabolism

Substances

  • Xanthines
  • Xanthine
  • Uric Acid
  • Manganese
  • Allopurinol
  • Dopamine
  • Norepinephrine