Neuroprotective effect of resveratrol on arsenic trioxide-induced oxidative stress in feline brain

Hum Exp Toxicol. 2014 Jul;33(7):737-47. doi: 10.1177/0960327113506235. Epub 2013 Oct 9.

Abstract

Arsenic trioxide (As2O3) is a known environmental toxicant and potent chemotherapeutic agent. Significant correlation has been reported between arsenic exposure (including consumption of arsenic-contaminated water and clinical use of As2O3) and dysfunction in the nervous system. In this study, we aimed to elucidate the effect of resveratrol with neuroprotective activities on As2O3-induced oxidative damage and cerebral cortex injury. Twenty-four healthy Chinese Dragon Li cats of either sex were randomly divided into four groups: control (1 ml/kg physiological saline), As2O3 (1 mg/kg), resveratrol (3 mg/kg) and As2O3 (1 mg/kg) + resveratrol (3 mg/kg). As2O3+resveratrol-treated group were given resveratrol (3 mg/kg) 1 h before As2O3 (1 mg/kg) administration. Pretreatment with resveratrol upregulated the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the level of reduced glutathione and the ratio of reduced glutathione to oxidised glutathione, and accumulation of arsenic in the cerebral cortex. These findings support neuroprotective effect of resveratrol on As2O3 toxicity in feline brain and provide a better understanding of the mechanism that resveratrol modulates As2O3-induced oxidative damage and a stronger rational for clinical use of resveratrol to protect brain against the toxicity of arsenic.

Keywords: Arsenic trioxide; brain; neuroprotective effect; oxidative damage; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Antioxidants / pharmacology*
  • Arsenic Trioxide
  • Arsenicals
  • Cats
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / enzymology
  • Cytoprotection
  • Environmental Pollutants / toxicity*
  • Female
  • Glutathione / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxides / toxicity*
  • Reactive Oxygen Species / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Arsenicals
  • Environmental Pollutants
  • Neuroprotective Agents
  • Oxides
  • Reactive Oxygen Species
  • Stilbenes
  • Malondialdehyde
  • Glutathione
  • Resveratrol
  • Arsenic Trioxide