Luteolin and Thiosalicylate Inhibit HGCL2 and Thimerosal-Induced VEGF Release from Human Mast Cells

Abstract

HgCl2 is a known environmental neurotoxin, but is also used as preservative in vaccines as thimerosal containing ethyl mercury covalently linked to thiosalicylate. We recently reported that mercury chloride (HgCl2) 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 μM 326±12 pg/106 cells and 335.5±12 pg/106 cells at 10 μM) compared to control cells (242±21 pg/106 cells, n=5, p<0.05); this effect is weaker than that induced by HgCl2 at 10 μM (448±14 pg/106 cells) (n=3, p<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 μM) added together with the peptide Substance P (SP) at 2 μM, used as a positive control, reduced VEGF release by 90%. Methyl thiosalicylate (1 or 10 μM) added with either SP or HgCl2 (10 μM) inhibited VEGF release by 100%, while sodium salicylate or ibuprofen had no effect. Pretreatment for 10 min with the flavonoid luteolin (0.1 mM) before HgCI2 or thimerosal completely blocked their effect. Luteolin and methyl thiosalicylate may be useful in preventing mercury-induced toxicity.