Human exposure to metal-containing substances happens through the environment and/or medical treatments, making it important to understand what these compounds do once inside the body. One such substance is thimerosal (THI), a mercury-based bactericidal that has been used as a preservative in vaccines globally since the 1950s to prevent bacterial growth in vaccine vials during storage. Scientists are still working to understand how THI behaves after entering human cells, especially under normal biological conditions.
Manon Fanny Degorge, Silas Mertz, and Professor Jürgen Gailer from the University of Calgary set out to explore this question in detail. Their study, published in the peer-reviewed journal Inorganics, looks at how THI interacts with naturally occurring biomolecules in the body, specifically L-glutathione and L-cysteine. These two biomolecules are commonly found inside cells and play important roles in maintaining normal cellular function, meaning they help keep cells stable and healthy. By using advanced laboratory methods, the researchers examined how THI reacts with these biomolecules under conditions similar to those in the human body.
Professor Gailer and his team found that THI does not stay unchanged when it comes into contact with L-glutathione. Instead, it quickly reacts to form a new compound that is comprised of L-glutathione and a mercury-containing breakdown product of THI. Professor Gailer said, “When THI was passed through the chromatography column with L-glutathione dissolved in the mobile phase, we observed the formation of a new mercury compound which eluted before THI”. A fraction of this novel mercury-containing metabolite was analyzed by ESI-MS and revealed the formation of an ethylmercury-L-glutathione complex. The term metabolite refers to a new chemical compound that is formed when two substances – in this case L-glutathione and THI – react with each other.
Professor Gailer’s research team observed similar results when L-cysteine – which is an amino acid that is commonly found in mammalian cells – was dissolved in the mobile phase. Taken together these results suggest that both biomolecules play a crucial role in breaking down THI in the body, though they may do so at slightly different speeds because of their different structures and availability.
To make sure these findings were accurate, Professor Gailer and his team used a complementary method to confirm the chemical reaction, namely 199Hg nuclear magnetic resonance spectroscopy. The latter method allows to observe changes in the environment around a metal – mercury in the case of THI – during its involvement in a chemical reaction. All results pointed to the same conclusion: THI reacts directly with these naturally occurring biomolecules. Professor Gailer added, “Our results show that L-glutathione and L-cysteine, natural biomolecules found inside cells, react with THI under normal conditions found in the human body,” reinforcing that the uncovered interactions are likely to happen under normal conditions inside human cells.
Understanding this process is important because L-glutathione plays a vital role in protecting cells and keep them functioning properly by preventing damage. The newly formed ethylmercury-L-glutathione containing metabolite will behave differently in the body compared to THI. Importantly, the formation of this novel metabolite could help explain previously observed effects of THI on certain cellular systems, including the blocking of calcium channels which play an important role in the homeostasis of Ca2+.
Overall, Professor Gailer’s study provides clearer insight into the likely first step of what happens to THI after it enters the body. By showing that THI can quickly react with common biomolecules found inside cells, the researchers provide valuable insight into its biochemical behavior. While further research is needed to confirm if these reactions occur in complex biological environments (e.g. inside red blod cells), the findings help to design follow up experiments to delineate as to what happens when the ethylmercury-L-glutathione complex reacts with proteins within human cells of the body.
Journal Reference
Degorge M.F., Mertz S., Gailer J. “Degradation of the Vaccine Additive Thimerosal by L-Glutathione and L-Cysteine at Physiological pH.” Inorganics, 2025; 13: 280. DOI: https://doi.org/10.3390/inorganics13090280
