Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: reversal effect of essential metals and a chelating agent

Environ Toxicol Pharmacol. 2013 Nov;36(3):1150-66. doi: 10.1016/j.etap.2013.09.021. Epub 2013 Oct 11.

Abstract

Arsenic (As) widely studied for its effects as a neurotoxicant. The present study was designed to evaluate the protective effect of calcium, zinc or monoisoamyl dimercaptosuccinic acid (MiADMSA), either individually or in combination on As induced oxidative stress and apoptosis in brain regions (cerebral cortex, hippocampus and cerebellum) of postnatal day (PND) 21, 28 and 3 months old rats. Arsenic exposure significantly decreased the activities of superoxide dismutase (SOD) isoforms, catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) with increase in glutathione s transferase (GST) while lipid peroxidation (LPx), arsenic levels, mRNA expression of caspase 3 and 9 were significantly increased in different brain regions. Arsenic induced alterations in these parameters were greater in PND 28 and more pronounced in cerebral cortex. From the results it is evident that combined supplementation of calcium and zinc along with MiADMSA would be most effective compared to individual administration in reducing arsenic induced neurotoxicity.

Keywords: Apoptosis; Arsenic toxicity; Brain regions; Calcium and zinc supplementation; Chelation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Apoptosis / drug effects*
  • Arsenic / toxicity*
  • Brain / drug effects
  • Brain / enzymology*
  • Calcium / pharmacology
  • Caspases / metabolism*
  • Chelating Agents / pharmacology*
  • Lipid Peroxidation / drug effects
  • Metals / metabolism
  • Metals / pharmacology*
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Succimer / analogs & derivatives
  • Succimer / pharmacology
  • Zinc / pharmacology

Substances

  • Antioxidants
  • Chelating Agents
  • Metals
  • monoisoamyl-2,3-dimercaptosuccinate
  • Succimer
  • Caspases
  • Zinc
  • Arsenic
  • Calcium