Ethanol via Regulation of NF-κB/p53 Signaling Pathway Increases Manganese-Induced Inflammation and Apoptosis in Hypothalamus of Rats

  • Kpobari W. NkpaaEmail author
  • Isaac A. Adedara
  • Benjamin A. Amadi
  • Matthew O. Wegwu
  • Ebenezer O. FarombiEmail author


The diet is a major route of manganese (Mn) exposure for humans. Interestingly, several epidemiological data demonstrated an increase in the incidence of alcohol consumption globally. Chemical-chemical interaction subsequent to chemical mixtures exposure may result in a synergism or antagonism effects. The present study investigated the influence of co-exposure to ethanol (EtOH) and Mn on inflammation and apoptosis in the hypothalamus of rats. The study consisted of five groups of rats that were exposed to drinking water alone, EtOH alone at 5 g/kg, Mn alone at 30 mg/kg or co-expose with EtOH at 1.25 and 5 g/kg body weight by oral gavage for 35 consecutive days. The results indicated that the significant (p < 0.05) increases in pro–inflammatory cytokines, namely tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) as well as cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) activation in the hypothalamus following individual exposure to Mn and EtOH to rats were intensified in the co-exposure group. Moreover, immunohistochemistry analysis showed marked decrease in B cell lymphoma-2 (Bcl-2) protein expression as well as the increases in the apoptotic proteins, namely Bax and caspase-3 along with p53 in the hypothalamus of rats treated with Mn or EtOH alone were intensified in the co-exposure group. Taken together, these findings highlight that EtOH exacerbated the induction of inflammatory and apoptotic biomarkers via regulation of NF-κB/p53 signaling pathways in the hypothalamus of rats. These alterations may have profound disrupting effects on the hypothalamus functions such as impairment of it metabolic and autonomic nervous system functions.


Ethanol Manganese Inflammation Apoptosis NF-κB/p53 signaling pathways 



This research was done without specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

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

Authors and Affiliations

  • Kpobari W. Nkpaa
    • 1
    Email author
  • Isaac A. Adedara
    • 2
  • Benjamin A. Amadi
    • 1
  • Matthew O. Wegwu
    • 1
  • Ebenezer O. Farombi
    • 2
    Email author
  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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