Dietary supplementation with (R)-α-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex

Abstract

Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24-28-month-old rats were increased by 80% (p<0.01) relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because (R)-alpha-Lipoic acid (LA) is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding LA (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old LA-fed rats versus controls. These results thus show that LA supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.

The Thiol Antioxidant Lipoic Acid and Alzheimer’s Disease

“…Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats. These results thus show that chronic LA supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging (Suh et al 2005). Since amyloid aggregates have been shown to be stabilized by transition metals such as iron and copper, it was also speculated that LA could inhibit aggregate formation or potentially dissolve existing amyloid deposits.…”

“…Furthermore, the abnormal combination of Ab with iron or copper ions induces the production of hydrogen peroxide from molecular oxygen (Huang et al 1999), which subsequently produces the neurotoxic hydroxyl radical by Fenton or Haber-Weiss reactions. Because LA is a potent chelator of divalent metal ions in vitro, the effect of a RLA inclusive diet on cortical iron levels and antioxidant status was investigated in aged rats (Suh et al 2005). Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats.…”

Age Associated Fluoride Induced Ultra Structural and Biochemical Changes in Rat Brain

“…Fluoride administration is known to cause oxidative modification of proteins, lipids and DNA [24] and increased lipofuscin concentration could deleteriously affect the neurons, leading to depletion of antioxidants status [25]. The brain is known to possess many antioxidant enzymes; among them SOD plays a major role as it prevents ROS mediated tissue damage [26].…”

Alpha Lipoic Acid (AlA) Combining with Corticosteroid Hormone Improves the Outcome of Infectious Diseases in Spinal Cord (10 Cases Study)

“…The remarkable discovery of ALA pharmacological roles are that reverse the age-related accumulation of iron in the rat cerebral cortex [11], improve endothelial function [12], and increase insulin sensitivity in patients with diabetes [13], which imply ALA's intervention role in mitochondria. Therefore, ALA has potential capability to recover the function of Brain blood barrier (BBB) in injured CNS.…”