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

Bibliographic

Year of Publication:
2005
Contact PI Name:
Rajadas Jayakumar
Contact PI Affiliation:
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, India
Co-Authors:
E. Philip Jesudason, J. Gunasingh Masilamoni, K. Samuel Jesudoss
Primary Reference (PubMED ID):
Funding Source:
Council of Scientific and Industrial Research (CSIR) India
Indian Council for Medical Research
Study Goal and Principal Findings:

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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 25-35
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
alpha-Lipoic Acid (ALA)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
Non-transgenic
Strain/Genetic Background:
Swiss

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
Activated Astrocytes
Biochemical
Catalase (CAT) Activity
Glutathione Peroxidase (GPx) Activity
Superoxide Dismutase (SOD) Activity
ATPase
Glutathione (GSH)
Lipid Peroxidation
Reactive Oxygen Species (ROS)
Thiobarbituric Acid Reactive Substances (TBARS)
Immunochemistry
Activated Astrocytes
Toxicology
Body Weight
Organ Weight
Organ Histopathology