Menadione increases hepatic tight-junctional permeability. Its effect can be decreased by butylated hydroxytoluene and verapamil.
Infusion of menadione at two different doses [2.7 mg and 5.5 mg in 100 microliters of dimethyl sulphoxide (DMSO)] into perfused rat livers for 30 min caused no or a 6-fold increase respectively in junctional permeability to horseradish peroxidase as compared with controls receiving 100 microliters of DMSO alone. The total glutathione (GSH) contents in these livers measured at the end of the experiments were 115% and 53%, compared with the controls. The free-radical scavenger butylated hydroxytoluene (BHT) (final concn. 5 microM) protected against the GSH depletion caused by the higher dose of menadione and partially decreased the menadione-induced increase in junctional permeability. Verapamil, a Ca2(+)-channel blocker which was added into the perfusion medium (final concn. 40 microM) 10 min before the infusion of 5.5 mg of menadione, completely abolished the effect of menadione on junctional permeability. Menadione exposure therefore increases tight-junctional permeability in the liver; this may involve a depletion of GSH and a subsequent increase in intracellular Ca2+.
School of Biochemistry, University of Birmingham, U.K.
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Coleman
D000818:Animals; D001646:Bile / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D007365:Intercellular Junctions / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology*
D014812:Vitamin K; D002084:Butylated Hydroxytoluene; D014700:Verapamil; D006735:Horseradish Peroxidase; D005978:Glutathione