The protective role of DL-alpha-lipoic acid in the oxidative vulnerability triggered by Abeta-amyloid vaccination in mice

Mol Cell Biochem. 2005 Feb;270(1-2):29-37. doi: 10.1007/s11010-005-3301-z.

Abstract

Recent reports indicate that beta-amyloid peptide (Abeta) vaccine based therapy for Alzheimer's disease (AD) may be on the horizon. There are however, concerns about the safety of this approach. Immunization with Abeta has several disadvantages, because it crosses the blood brain barrier and cause inflammation and neurotoxicity. The present work is aimed to study the protective effective of alpha-lipoic acid (LA) in the oxidative vulnerability of beta-amyloid in plasma, liver, spleen and brain, when Abeta fibrils are given intraperitoneally in inflammation induced mice. Result shows that reactive oxygen species (ROS) in the astrocytes of inflammation induced mice along with Abeta (IA) has shown 2.5-fold increase when compared with LA treated mice. The increased level of lipid peroxidase (LPO) (p < 0.05) and decreased antioxidant status (p < 0.05) were observed in the plasma, liver, spleen and brain of LA induced mice when compared with LA treated mice. Data shows that there were no significant changes observed between the control and LA treated mice. Our biochemical and histological results highlight that significant oxidative vulnerability was observed in IA treated mice, which was prevented by LA therapy. Our findings suggest that the antioxidant effect of LA when induced with Abeta may serve as a potent therapeutic tool for inflammatory AD models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / genetics*
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Astrocytes / chemistry
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Body Weight
  • Brain / metabolism
  • Cancer Vaccines*
  • Catalase / metabolism
  • Cells, Cultured
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Inflammation
  • Lipid Peroxidation
  • Liver / metabolism
  • Mice
  • Models, Chemical
  • Organ Size
  • Oxygen / metabolism*
  • Peptide Fragments / chemistry
  • Reactive Oxygen Species
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Spleen / metabolism
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Thioctic Acid / metabolism
  • Thioctic Acid / pharmacology*
  • Tissue Distribution

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Cancer Vaccines
  • Peptide Fragments
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • amyloid beta-protein (25-35)
  • Thioctic Acid
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Adenosine Triphosphatases
  • Sodium-Potassium-Exchanging ATPase
  • Glutathione
  • Oxygen