Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain

Can J Physiol Pharmacol. 2012 May;90(5):595-606. doi: 10.1139/y2012-030. Epub 2012 Apr 4.

Abstract

The present investigation was designed to determine the efficacy of Bacopa monnieri (Brahmi; BM) to offset 3-nitropropionic acid (3-NPA) induced oxidative stress and mitochondrial dysfunction in dopaminergic (N27) cells and prepubertal mouse brain. Pretreatment of N27 cells with BM ethanolic extract (BME) significantly attenuated 3-NPA-induced cytotoxicity. Further, we determined the degree of oxidative stress induction, redox status, enzymic antioxidants, and protein oxidation in the striatal mitochondria of mice given BME prophylaxis followed by 3-NPA challenge. While 3-NPA-induced marked oxidative stress in the mitochondria of the striatum, BME prophylaxis markedly prevented 3-NPA-induced oxidative dysfunctions and depletion of reduced glutathione and thiol levels. The activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, thioredoxin reductase), Na(+),K(+)-ATPase, and citric acid cycle enzymes in the striatum discernible among 3-NPA mice were significantly restored with BME prophylaxis. Interestingly, BME offered protection against 3-NPA-induced mitochondrial dysfunctions as evidenced by the restoration of the activities of ETC enzymes (NADH:ubiquinone oxidoreductase, NADH:cytochrome c reductase, succinate-ubiquinone oxidoreductase, and cytochrome c oxidase) and mitochondrial viability. We hypothesize that the neuroprotective effects of BME may be wholly or in part related to its propensity to scavenge free radicals, maintain redox status, and upregulate antioxidant machinery in striatal mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Bacopa / chemistry*
  • Cell Line
  • Citric Acid Cycle / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology
  • Electron Transport / drug effects
  • Electron Transport Chain Complex Proteins / metabolism
  • Free Radical Scavengers / pharmacology
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Male
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondria / physiology
  • Neuroprotective Agents / pharmacology
  • Nitro Compounds
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • Propionates
  • Rats
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Superoxide Dismutase / metabolism
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Antioxidants
  • Electron Transport Chain Complex Proteins
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Nitro Compounds
  • Plant Extracts
  • Propionates
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Thioredoxin-Disulfide Reductase
  • Sodium-Potassium-Exchanging ATPase
  • Glutathione
  • 3-nitropropionic acid