Menadione increases hepatic tight-junctional permeability. Its effect can be decreased by butylated hydroxytoluene

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K S Kan1, R Coleman

  • 1School of Biochemistry, University of Birmingham, U.K.

The Biochemical Journal
|August 15, 1990
PubMed

Insights

Menadione infusion increases liver junctional permeability, potentially via glutathione depletion and calcium influx. Butylated hydroxytoluene and verapamil offer protective effects against menadione toxicity.

Area of Science:

  • Hepatology
  • Cell biology
  • Toxicology

Background:

  • Menadione, a vitamin K analog, is known to induce oxidative stress.
  • Liver tight junctions regulate paracellular transport and are crucial for liver function.

Purpose of the Study:

  • To investigate the effect of menadione on liver junctional permeability.
  • To explore the mechanisms underlying menadione-induced changes in liver permeability, including the roles of glutathione and calcium.

Main Methods:

  • Perfused rat liver model was used to study menadione infusion.
  • Horseradish peroxidase was used as a tracer to assess junctional permeability.
  • Glutathione levels were measured, and the effects of butylated hydroxytoluene and verapamil were evaluated.

Main Results:

  • Menadione significantly increased liver junctional permeability in a dose-dependent manner.
  • Menadione caused a depletion of total glutathione (GSH) in liver cells.
  • Butylated hydroxytoluene partially protected against menadione's effects, while verapamil completely abolished the increase in permeability.

Conclusions:

  • Menadione exposure increases liver tight-junctional permeability.
  • This effect may involve menadione-induced depletion of GSH and subsequent intracellular calcium increase.
  • Calcium channel blockers like verapamil can mitigate menadione-induced permeability changes.

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