Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells.
HgCl2 is a known environemental neurotoxin, but is also used as preservative in vaccines as thimerosal containing ethyl mercury covalently linked to thiosalicylate. We recently reported that mercury choloride (HgCl(2)) can stimulate human mast cells to release vascular endothelial growth factor (VEGF), which is also vasoactive and pro-inflammatory. Here we show that thimerosal induces significant VEGF release from human leukemic cultured LAD2 mast cells (at 1 microM 326 ± 12 pg/106 cells and 335.5 ± 12 pg/106 cells at 10 microM) compared to control cells (242 ± 21 pg/106 cells, n=5, p less than 0.05); this effect is weaker than that induced by HgCl2 at 10 microM (448 ± 14 pg/106 cells) (n=3, p less than 0.05). In view of this finding, we hypothesize that the thiosalicylate component of thimerosal may have an inhibitory effect on VEGF release. Thimerosal (10 microM) added together with the peptide Substance P (SP) at 2 microM, used as a positive control, reduced VEGF release by 90 percent. Methyl thiosalicylate (1 or 10 microM) added with either SP or HgCl2 (10 microM) inhibited VEGF release by 100 percent, while sodium salicylate or ibuprofen had no effect. Pretreatment for 10 min with the flavonoid luteolin (0.1 mM) before HgCl2 or thimerosal compeletly blocked their effect. Luteolin and methyl thiosalicylate may be useful in preventing mercury-induced toxicity.
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA.
S
S
Asadi
B
B
Zhang
Z
Z
Weng
A
A
Angelidou
D
D
Kempuraj
K D
KD
Alysandratos
T C
TC
Theoharides
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity*; D012459:Salicylates / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013849:Thimerosal / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D012459:Salicylates; D013438:Sulfhydryl Compounds; D042461:Vascular Endothelial Growth Factor A; D013849:Thimerosal; D013373:Substance P; D008627:Mercuric Chloride; C441201:thiosalicylic acid; D047311:Luteolin