Zinc protects against tumor necrosis factor-induced disruption of porcine endothelial cell monolayer integrity

B. Hennig, Y. Wang, S. Ramasamy, C. J. McClain

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Some nutrients influence the metabolic response of cytokines such as tumor necrosis factor. Inadequate levels of the essential trace element zinc may play a role in tumor necrosis factor-induced disruption of the vascular endothelial barrier function. To test this hypothesis, endothelial cells cultured on polycarbonate filters or culture plates were exposed to six different treatments for 3 d: medium 199 enriched with 5% fetal bovine serum (control), control + two levels of supplemental zinc (7.7 and 12.3 μmol/L medium), tumor necrosis factor (5 x 105 u/L) and tumor necrosis factor + the two levels of Zn as noted previously. Endothelial barrier function, expressed as albumin transfer across cultured endothelial monolayers, was not affected by Zn enrichment alone. Tumor necrosis factor treatment significantly increased albumin transfer compared with control cultures. The lower concentration of Zn partially and the higher concentration totally prevented the tumor necrosis factor-induced increase in albumin transfer. The increase in cytosolic release of [3H]adenine (marker of cell injury) induced by tumor necrosis factor was prevented by added Zn. Tumor necrosis factor treatment significantly decreased angiotensin-converting enzyme activity, and tumor necrosis factor also decreased activities of two other membrane-bound enzymes, total ATPase and Ca2+-ATPase. These activities all were restored by Zn enrichment. Tumor necrosis factor treatment caused a decrease in cellular Zn concentration, which was prevented when the culture media were enriched with Zn. These data suggest that an important relationship exists between Zn status and tumor necrosis factor-induced endothelial cell dysfunction.

Original languageEnglish
Pages (from-to)1003-1009
Number of pages7
JournalJournal of Nutrition
Issue number6
StatePublished - 1993


  • cell injury
  • endothelial cell integrity
  • tumor necrosis factor
  • zinc
  • zinc supplementation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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