Diphenyl Diselenide Protects Against Mortality, Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity

Neurochem Res. 2016 Jun;41(6):1430-8. doi: 10.1007/s11064-016-1852-x. Epub 2016 Feb 15.

Abstract

Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure.

Keywords: Diphenyl diselenide (DPDS); Drosophila melanogaster; Manganese; Neurotoxicity; Oxidative stress.

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzene Derivatives / pharmacology*
  • Benzene Derivatives / therapeutic use
  • Disease Models, Animal*
  • Drosophila melanogaster
  • Manganese / toxicity*
  • Mortality / trends
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / mortality
  • Neurotoxicity Syndromes / prevention & control
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / therapeutic use
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Tabes Dorsalis / metabolism*
  • Tabes Dorsalis / mortality
  • Tabes Dorsalis / prevention & control*

Substances

  • Benzene Derivatives
  • Neuroprotective Agents
  • Organoselenium Compounds
  • Reactive Oxygen Species
  • diphenyldiselenide
  • Manganese