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.
Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1015-20. doi: 10.1177/039463201002300406.
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.
氯化汞（HgCl2）是一种已知的环境神经毒素，但也被用作含乙基汞的硫柳汞作为疫苗防腐剂，其与硫代水杨酸共价结合。我们最近报道氯化汞（HgCl(2)）可以刺激人肥大细胞释放血管内皮生长因子（VEGF），这也是血管活性和促炎的。在这里，我们表明硫柳汞（1 microM 时 326 ± 12 pg/106 细胞和 10 microM 时 335.5 ± 12 pg/106 细胞）比对照细胞（242 ± 21 pg/106 细胞，n=5，p 小于 0.05）显著诱导人白血病培养的 LAD2 肥大细胞释放 VEGF；这种作用比 10 microM 的 HgCl2（448 ± 14 pg/106 细胞）诱导的作用弱（n=3，p 小于 0.05）。鉴于这一发现，我们假设硫柳汞中的硫代水杨酸成分可能对 VEGF 释放具有抑制作用。10 microM 的硫柳汞与作为阳性对照的 2 microM 神经肽 P （Substance P，SP）一起添加时，VEGF 释放减少了 90%。1 或 10 microM 的甲基硫代水杨酸（methyl thiosalicylate）与 SP 或 HgCl2（10 microM）一起添加时，VEGF 释放被抑制了 100%，而水杨酸钠或布洛芬没有效果。在用 HgCl2 或硫柳汞预处理 10 分钟后，用黄酮类化合物木犀草素（0.1 mM）预处理完全阻断了它们的作用。木犀草素和甲基硫代水杨酸可能有助于预防汞诱导的毒性。
