Melatonin reduces oxidative neurotoxicity due to quinolinic acid: In vitro and in vivo findings

Javier Cabrera, Russel J. Reiter, Dun Xian Tan, Wenbo Qi, Rosa M. Sainz, Juan Carlos Mayo, Joaquin J. Garcia, Seok Joong Kim, Gamal El-Sokkary

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

The in vivo and in vitro effects of melatonin on quinolinic acid-induced oxidative damage in rat brain were determined. The concentrations of malonaldehyde and 4-hydroxyalkenals were assayed as an index of oxidatively damaged lipid. In in vitro experiments, the increase in malonaldehyde and 4-hydroxyalkenals concentrations induced by quinolinic acid were concentration-dependent and time-dependent. The accumulation of products of lipid peroxidation induced by quinolinic acid were very significantly reduced by melatonin in a concentration-dependent manner. Additionally, at the highest concentrations of melatonin used in quinolinic acid treated homogenates, it reduced the levels of oxidatively damaged lipid products below those measured in control homogenates (no quinolinic acid or melatonin). When quinolinic acid (200 mg/kg) was intraperitonally injected into 11-day-old rats, lipid peroxidation in the brain was significantly increased 24 hours later compared to levels in control rats. When melatonin (10 mg/kg) was injected ip 30 min before and 4 and 20 hours after the administration of quinolinic acid, the increased lipid peroxidation induced by quinolinic acid was significantly reduced. Likewise, neurobehavioral signs associated with quinolinate administration were attenuated by melatonin. These results show that both in vitro and in vivo pharmacological levels of melatonin confer protection against quinolinic acid-induced oxidative toxicity in the brain. The findings also indicate that melatonin may be pharmacologically useful in combatting quinolinic neurotoxicity which is associated with several acute and chronic neurodegenerative neurological diseases. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)507-514
Number of pages8
JournalNeuropharmacology
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2000

    Fingerprint

Keywords

  • Brain
  • Free radicals
  • Lipid peroxidation
  • Melatonin
  • Neurotoxicity
  • Quinolinic acid

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Cabrera, J., Reiter, R. J., Tan, D. X., Qi, W., Sainz, R. M., Mayo, J. C., Garcia, J. J., Kim, S. J., & El-Sokkary, G. (2000). Melatonin reduces oxidative neurotoxicity due to quinolinic acid: In vitro and in vivo findings. Neuropharmacology, 39(3), 507-514. https://doi.org/10.1016/S0028-3908(99)00128-8