2014年12月18日星期四

Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

Abbreviations

  • As (III)arsenic
  • ROSreactive oxygen species
  • NOnitric oxide
  • ΔΨmMitochondrial membrane potential;
  • AO/EB stainingAcridine orange/Ethium bromide staining
  • MWMMorris Water Maze
  • GPxglutathione peroxidase activity
  • GSTglutathione S-Transferease
  • SODSuperoxide dismutase
  • Achacetyl choline;
  • TBARSThiobarbituric Acid Reactive Substances
  • GSH and GSSGReduced and Oxidized Glutathione

Keywords