Humans are being exposed to a variety of potentially toxic metal compounds through the diet and/or the intravenous administration of metal-containing medicinal drugs. The organomercurial thimerosal (THI) is a bactericidal that is present in vaccines, but its potential degradation by biomolecules in vivo is incompletely understood. To probe its interaction with low-molecular-weight thiols that are highly abundant within cells, we have employed an LC-based analytical approach in conjunction with a mercury-specific detector. The injection of THI into a C18-HPLC column equilibrated with mobile phases that contained increasing concentrations of up to 15 mM of glutathione (GSH) and 30% acetonitrile revealed the elution of a GS-EtHg adduct in conjunction with THI, as evidenced by electrospray ionization mass spectrometry. These results were confirmed by 199Hg-NMR spectroscopy. While these results imply a rapid degradation of THI by GSH at physiological pH, it is important to point out that our results were obtained in aqueous solutions containing 30% (v:v) acetonitrile. Further studies need to confirm if the GS-EtHg adduct is also formed in biological fluids. Our results nevertheless demonstrate that GSH and L-cysteine (Cys) are potential targets of THI at physiological pH, which is relevant to better understand its side effects, including previously reported effects on Ca2+ channels.
Degorge et al. (Sat,) studied this question.