Erythropoietin restores glutathione peroxidase activity in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine-induced neurotoxicity in C57BL mice and stimulates murine astroglial glutathione peroxidase production in vitro

Neurosci Lett. 2002 Mar 15;321(1-2):73-6. doi: 10.1016/s0304-3940(02)00041-1.


Recently, we have reported that erythropoietin (Epo) provides neuroprotection in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo. In the present study, we investigated the effects of single Epo administration on brain antioxidant enzyme (superoxide dismutase (SOD) and glutathion peroxidase (GSHPx)) activities in this model in C57BL/6 mice. We found that MPTP treatment decreased GSHPx activity in both substantia nigra and striatum, and Epo restores nigral GSHPx activity decreased by MPTP. SOD enzyme activity was not significantly changed by MPTP and Epo treatment. Further, Epo stimulated astroglial GSHPx production in neonatal murine astroglial cell culture suggesting that the possible cell source for the stimulation of GSHPx activity by Epo in the MPTP-induced neurotoxicity model are astroglia. In conclusion, modulation of the astroglial antioxidant defense system might be one of the mechanisms by which Epo exerts a beneficial effect in MPTP-induced Parkinsonism.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors*
  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / enzymology
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Erythropoietin / pharmacology*
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism*
  • Male
  • Mice
  • Neostriatum / drug effects
  • Neostriatum / enzymology
  • Neostriatum / physiopathology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / antagonists & inhibitors*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / physiopathology
  • Substantia Nigra / drug effects
  • Substantia Nigra / enzymology
  • Substantia Nigra / physiopathology
  • Superoxide Dismutase / metabolism


  • Neuroprotective Agents
  • Neurotoxins
  • Erythropoietin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Glutathione Peroxidase
  • Superoxide Dismutase