Zinc, a neuroprotective agent against aluminum-induced oxidative DNA injury

Mol Neurobiol. 2013 Aug;48(1):1-12. doi: 10.1007/s12035-013-8417-7. Epub 2013 Feb 19.


Aluminum (Al) has been considered as one of the most abundant elements and comprises nearly 8 % of the Earth's crust. Despite of its immense presence, studies regarding the molecular basis of its interaction with the physiological system are rather sparse. On the other hand, zinc (Zn), an essential micronutrient, has been regarded as the second most important metal for brain functioning. The objective of the present study was to investigate the protective potential of Zn, if any, during Al-induced detrimental effects on DNA, tritiated thymidine uptake as well as expression of stress marker genes and proteins in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups viz.: normal control, Al treated (100 mg/kg b wt/day via oral gavage), Zn treated (227 mg/l in drinking water), and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Agarose gel electrophoresis revealed DNA laddering pattern and comets in the rat brain following Al treatment, which however, were attenuated upon Zn treatment. Further, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, number of apoptotic brain cells, and uptake of tritiated thymidine were increased after Al treatment but were decreased upon Zn supplementation. Western blot and mRNA expressions of p53 and nuclear factor κB (NF-κB) were also found to be significantly elevated after Al treatment, which however, were reversed following Zn treatment. Hence, Zn shall prove to be an effective agent in mitigating the detrimental effects caused by Al in the rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum / toxicity*
  • Animals
  • Apoptosis / drug effects
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Cerebrum / drug effects
  • Cerebrum / metabolism
  • Comet Assay
  • DNA / isolation & purification
  • DNA Damage*
  • DNA Fragmentation / drug effects
  • Densitometry
  • Electrophoresis, Agar Gel
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Fluorescence
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Thymidine / metabolism
  • Tritium / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Zinc / pharmacology*


  • NF-kappa B
  • Neuroprotective Agents
  • Tumor Suppressor Protein p53
  • Tritium
  • DNA
  • Aluminum
  • Zinc
  • Thymidine