Ethanol Exacerbates Manganese-Induced Neurobehavioral Deficits, Striatal Oxidative Stress, and Apoptosis Via Regulation of p53, Caspase-3, and Bax/Bcl-2 Ratio-Dependent Pathway

  • Kpobari W. NkpaaEmail author
  • Ifeoluwa O. Awogbindin
  • Benjamin A. Amadi
  • Amos O. Abolaji
  • Isaac A. Adedara
  • Matthew O. WegwuEmail author
  • Ebenezer O. Farombi


This study investigated the effects of ethanol (EtOH) on manganese (Mn)-induced striatal toxicity in rat by evaluating the neurobehavioral changes, biochemical and molecular events in rats exposed to Mn alone at 30 mg/kg, or their combination with EtOH at 1.25- and 5-g/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were assessed using a video tracking software (ANY-Maze software) during a 5-min trial in a novel environment. Subsequently, acetylcholinesterase (AChE) activity, oxidative stress markers, histological morphology, and expression of apoptotic proteins (p53 and Bax and caspase-3) and anti-apoptotic protein (Bcl-2) were assessed in the striatum. Results showed that Mn, EtOH, and their combination induced locomotor and motor deficits. Track plot analysis indicated that EtOH exacerbated the Mn-induced reduction in exploratory profiles of exposed rats. Similarly, exposure of rats to Mn, EtOH, or combination of Mn and EtOH resulted in decreased activities of anti-oxidant enzymes, diminished level of reduced glutathione, downregulated Bcl-2 expression, increased AChE activity, enhanced hydrogen peroxide and lipid peroxidation levels, and upregulated expressions of p53, Bax, and caspase-3. Moreover, potentiation of Mn-induced striatal toxicity by EtOH co-exposure was dose dependent. Taken together, it seems that EtOH exacerbates Mn-induced neurobehavioral deficits, oxidative stress, and apoptosis induction via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway in rat striatum.


Manganese Ethanol Neurobehavioral deficits Oxidative stress Apoptosis Striatum 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Environmental Toxicology Unit, Department of Biochemistry, Faculty of ScienceUniversity of Port HarcourtChobaNigeria
  2. 2.Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of MedicineUniversity of IbadanIbadanNigeria

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