Protective effects of ascorbic acid against lead-induced apoptotic neurodegeneration in the developing rat hippocampus in vivo

Brain Res. 2007 Dec 14:1185:68-74. doi: 10.1016/j.brainres.2007.09.044. Epub 2007 Sep 26.

Abstract

Lead is a neurotoxin that affects the developing central nervous system and may potentially induce apoptotic cell death. We investigated the effect of ascorbic acid against lead-induced neurotoxicity in the developing rat hippocampus. Female Sprague-Dawley rats were divided into three groups: control group, lead-treated group and lead plus ascorbic acid-treated group. Lead (0.2% lead acetate) was administered to female rats during pregnancy and lactation, in their drinking water. During this period, rats in the lead plus ascorbic acid-treated group received 100 mg/kg/day ascorbic acid, orally. At the end of the treatment, neuronal damage, apoptosis and blood lead levels were determined and the levels of Bax and Bcl-2 were immunodetected in the hippocampus of 21-day-old male pups. Histopathological evaluation demonstrated that ascorbic acid significantly attenuates apoptosis in the developing hippocampus and also spares hippocampal CA1, CA3 and dentate gyrus (DG) neurons. Simultaneous administration of ascorbic acid and lead lowered the level of Bax protein and increased Bcl-2 in pup hippocampus and reduced lead level in blood of dams compared with lead-treated only. Based on these results, it seems that ascorbic acid may potentially be beneficial in treating lead-induced brain injury in the developing rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Ascorbic Acid / therapeutic use*
  • Disease Models, Animal
  • Drug Interactions
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Hippocampus / ultrastructure
  • In Situ Nick-End Labeling / methods
  • Lead / toxicity
  • Lead Poisoning / complications
  • Male
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology*
  • Nerve Degeneration / prevention & control*
  • Neuroprotective Agents / therapeutic use*
  • Pregnancy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Lead
  • Ascorbic Acid