High dose selegiline augments striatal ubiquinol in mouse: an indication of decreased oxidative stress or of interference with mitochondrial respiration? A pilot study

J Neural Transm Suppl. 1995:46:149-56.

Abstract

The effects of unspecific doses of the irreversible monoamine oxidase inhibitor selegiline on alpha-tocopherol, alpha-tocopherolquinone, ubiquinol and ubiquinone were studied in frontal cortex, hippocampus and striatum of male C57BL/6 mice 4 h and 96 h after a single or six injections of selegiline (100 mg/kg body weight, i.p.), respectively. Inhibition of monoamine oxidase was confirmed by activity measurements of its isoforms A and B in brain stem nuclei and striatum as well as by determination of striatal levels of dopamine and its major metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. In general, levels of alpha-tocopherol were not altered and levels of alpha-tocopherolquinone were below the detection limit. However, 96 h following selegiline, levels of ubiquinols 9 and 10 were significantly increased, whereas levels of ubiquinones 9 and 10 concomitantly decreased in the striatum. Concentrations of ubiquinols and ubiquinones in frontal cortex and hippocampus were unchanged 96 h following selegiline. These data suggest that selegiline affects the striatal redox ratio of ubiquinol to ubiquinone which is important for cellular antioxidant defense and mitochondrial electron transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • Dose-Response Relationship, Drug
  • Homovanillic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxygen Consumption / drug effects
  • Pilot Projects
  • Selegiline / pharmacology*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / metabolism

Substances

  • Monoamine Oxidase Inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • Ubiquinone
  • Selegiline
  • ubiquinol
  • Homovanillic Acid