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Molybdenum bupropion combined neurotoxicity in rats

A M Helaly1, Naglaa Mokhtar2, Alaa El-Din L Firgany3

  • 1Forensic and Clinical Toxicology Department, Egypt; Faculty of Medicine, Yarmouk University, Jordan.

Regulatory Toxicology and Pharmacology : RTP
|August 7, 2018
PubMed

Insights

Combining the antidepressant bupropion with molybdenum, a heavy metal, proved highly toxic in animal models, causing significant fatalities. Bupropion demonstrated antioxidant and anti-inflammatory effects, but paradoxically, the combination led to severe intoxication and brain abnormalities.

Area of Science:

  • Toxicology
  • Neuroscience
  • Pharmacology

Background:

  • Heavy metal toxicity, particularly from molybdenum, poses a significant foodborne health risk in Egypt.
  • Molybdenum toxicity is understood to operate through oxidative-inflammatory pathways.
  • Bupropion, an antidepressant, possesses antioxidant properties and may offer protection against certain toxicities.

Purpose of the Study:

  • To investigate the toxicological effects of combining bupropion with molybdenum in an animal model.
  • To assess the potential cytoprotective or synergistic toxic effects of this drug-metal interaction.

Main Methods:

  • Administration of bupropion and varying doses of molybdenum to a toxic animal model.
  • Evaluation of oxidative stress and inflammation markers using ELISA assays for malondialdehyde (MDA), reduced glutathione, and interleukin-6 (IL-6).
  • Analysis of gene expression for nuclear factor erythroid 2-related factor 2 (Nrf2) and tumor necrosis factor-α (TNF-α) via real-time PCR.
  • Immunohistochemical examination of nuclear factor Kappa Beta (NF-κB) and histological analysis of brain tissue.

Main Results:

  • The combination of bupropion and high-dose molybdenum resulted in extreme toxicity and significant animal mortality.
  • Bupropion exhibited antioxidant and anti-inflammatory effects, reducing MDA and IL-6 levels and modulating Nrf2 and TNF-α gene expression.
  • Bupropion mitigated molybdenum-induced neuroinflammation, as evidenced by reduced NF-κB activity.
  • Histological examination revealed bupropion-induced choroid plexus hyperplasia and combined bupropion-molybdenum-induced choroid plexus papilloma.

Conclusions:

  • The combination of bupropion and molybdenum is highly toxic, leading to severe intoxication and fatalities, despite bupropion's observed anti-inflammatory and antioxidant effects.
  • Bupropion itself demonstrated toxicity at normal doses, causing choroid plexus hyperplasia.
  • The study highlights potential risks of drug-metal interactions, particularly concerning neuropathology and the long-term safety of antidepressants.
  • Further extensive research is crucial to understand these complex interactions and ensure the safety of antidepressant medications.
Keywords:
AntidepressantBrainBupropionInflammatory responseMolybdenumNrf2Oxidative stressTNF-α

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