Effects of indole-3-carbinol on clonidine-induced neurotoxicity in rats: Impact on oxidative stress, inflammation, apoptosis and monoamine levels

Neurotoxicology. 2014 Sep:44:48-57. doi: 10.1016/j.neuro.2014.05.004. Epub 2014 May 27.

Abstract

The relationship between inflammation, oxidative stress and the incidence of depression had been well studied. Indole-3-carbinol (I3C), a natural active compound found in cruciferous vegetables, was shown to have anti-oxidant and anti-inflammatory activities. Therefore, the aim of this study was to investigate the potential protective effects of I3C against clonidine-induced depression-like behaviors in rats. Also, the possible mechanisms underlying this neuroprotection; anti-oxidant, anti-inflammatory as well as the modulatory effect on monoamine levels in brain tissues were investigated. I3C was given orally (50mg/kg) daily over 2 weeks starting 7 days before giving clonidine (0.8mg/kg i.p.). Fluoxetine was used as a standard anti-depressant. Open-field test and forced swimming test were carried out to assess exploratory activity and despair behavior, respectively. I3C showed a significant improvement in the behavioral changes induced by clonidine. As indicators of oxidative stress, clonidine induced a significant reduction in GSH and SOD levels as well as an increase lipid peroxidation level. Tissue levels of pro-inflammatory and apoptotic markers were significantly increased in clonidine group. In addition, monoamine levels; noradrenaline and serotonin, showed a drastic decrease in clonidine group. Also, neuron specific enolase (NSE) was significantly elevated in clonidine group. In contrast, I3C pre-treatment significantly attenuated clonidine-induced oxidative stress, inflammation, apoptosis, decreased NSE expression and increased levels of monoamines. Fluoxetine was used as a standard. In conclusion, the findings of this study suggest that I3C protects against clonidine-induced depression. This neuroprotective effect is partially mediated by its anti-oxidant, anti-inflammatory and anti-apoptotic activities as well as elevating monoamines levels.

Keywords: Depression; Indole-3-carbinol; Inflammation; Monoamine; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Biogenic Monoamines / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Clonidine / toxicity
  • Depression / chemically induced
  • Depression / drug therapy*
  • Indoles / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Motor Activity / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Phosphopyruvate Hydratase / metabolism
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biogenic Monoamines
  • Indoles
  • Neuroprotective Agents
  • indole-3-carbinol
  • Phosphopyruvate Hydratase
  • Clonidine