Cell Biology and Toxicology

, Volume 29, Issue 2, pp 75–84 | Cite as

How aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale

  • Sungwon Han
  • Joseph Lemire
  • Varun P. Appanna
  • Christopher Auger
  • Zachary Castonguay
  • Vasu D. AppannaEmail author
Review Article


Metal pollutants are a global health risk due to their ability to contribute to a variety of diseases. Aluminum (Al), a ubiquitous environmental contaminant is implicated in anemia, osteomalacia, hepatic disorder, and neurological disorder. In this review, we outline how this intracellular generator of reactive oxygen species (ROS) triggers a metabolic shift towards lipogenesis in astrocytes and hepatocytes. This Al-evoked phenomenon is coupled to diminished mitochondrial activity, anerobiosis, and the channeling of α-ketoacids towards anti-oxidant defense. The resulting metabolic reconfiguration leads to fat accumulation and a reduction in ATP synthesis, characteristics that are common to numerous medical disorders. Hence, the ability of Al toxicity to create an oxidative environment promotes dysfunctional metabolic processes in astrocytes and hepatocytes. These molecular events triggered by Al-induced ROS production are the potential mediators of brain and liver disorders.


Aluminum toxicity Reactive oxygen species Mitochondrial dysfunction Dyslipidemia α-ketoacids Neurological and hepatic diseases 



Betaine-aldehyde dehydrogenase


γ-butyrobetaine dioxygenase


Electron transport chain


High-density lipoprotein


Hypoxia-inducible factor


3-hydroxy-N 6-trimethyllysine


Isocitrate dehydrogenase


Alpha-ketoglutarate dehydrogenase


Low-density lipoprotein


Malate dehydrogenase


Prolyl hydroxylase


Reactive oxygen species


Tricarboxylic acid


N 6-trimethyllysine


Trimethyllysine dioxygenase


Very-low-density lipoprotein



This work was supported by the Laurentian University and Industry Canada. Joseph Lemire was a recipient of the Alexander Graham Bell Canadian Graduate Scholarship (NSERC) and currently holds an NSERC-PDF, Christopher Auger is a recipient of the NSERC PGS-D.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Sungwon Han
    • 1
  • Joseph Lemire
    • 2
  • Varun P. Appanna
    • 1
  • Christopher Auger
    • 1
  • Zachary Castonguay
    • 1
  • Vasu D. Appanna
    • 1
    Email author
  1. 1.Department of Chemistry and BiochemistryLaurentian UniversitySudburyCanada
  2. 2.Department of Biological SciencesUniversity of CalgaryCalgaryCanada

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