Biphasic effects of dithiocarbamates on the activity of nuclear factor-kappaB

Eur J Pharmacol. 2000 Mar 31;392(3):133-6. doi: 10.1016/s0014-2999(00)00109-6.


Dithiocarbamates are well-known antioxidants and nuclear factor-kappaB (NF-kappaB) inhibitors. Recently, they have been characterized as zinc ionophores. Concentration-dependent biphasic effects of dithiocarbamates on NF-kappaB activity have been widely reported. We studied the mechanism of this phenomenon in relation to Zn(2+) influx. Two dithiocarbamates, pyrrolidine dithiocarbamate and diethyldithiocarbamate, showed concentration-dependent biphasic effects in inhibiting NF-kappaB activation in cerebral endothelial cells. These unique effects of dithiocarbamates on NF-kappaB were tightly linked to their ability to elevate intracellular Zn(2+)500 microM), dithiocarbamates started to lose their ability to promote Zn(2+) influx and to inhibit NF-kappaB activation. These results might provide insight into the appropriate use of dithiocarbamates in various disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Cerebral Cortex / blood supply
  • Ditiocarb / pharmacology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • Pyrrolidines / pharmacology*
  • Thiocarbamates / pharmacology*
  • Zinc / metabolism
  • Zinc / pharmacokinetics


  • NF-kappa B
  • Pyrrolidines
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid
  • Ditiocarb
  • Zinc