title: Effects of indole-3-carbinol on clonidine-induced neurotoxicity in rats: Impact on oxidative stress, inflammation, apoptosis and monoamine levels.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: reemelnaga@hotmail.com.
authors.forename: Reem N
authors.initials: RN
authors.lastname: El-Naga
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Hebatalla I
authors.initials: HI
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Ekram N
authors.initials: EN
authors.lastname: Abd Al Haleem
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003000:Clonidine / Q000633:toxicity; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015306:Biogenic Monoamines; D007211:Indoles; D018696:Neuroprotective Agents; C016517:indole-3-carbinol; D010751:Phosphopyruvate Hydratase; D003000:Clonidine
keywords: Depression; Indole-3-carbinol; Inflammation; Monoamine; Oxidative stress