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Low molecular weight thiols reduce thimerosal neurotoxicity in vitro: modulation by proteins
E Zieminska1, B Toczylowska, A Stafiej
1Mossakowski Medical Research Centre Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. elkaz@cmdik.pan.pl
Toxicology
|August 11, 2010
Summary
Thimerosal (TH) neurotoxicity in rat cerebellar cells was reduced by sulfur-containing compounds like cysteine and glutathione. These compounds, along with serum proteins, protected cells from TH-induced damage by interacting with ethylmercury.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Thimerosal (TH), an ethylmercury preservative in vaccines, exhibits in vitro neurotoxicity.
- Mercury's affinity for thiol groups is known, but the protective role of proteins and amino acids against TH neurotoxicity requires further investigation.
Purpose of the Study:
- To investigate the protective effects of serum proteins and sulfur-containing amino acids against Thimerosal-induced neurotoxicity in primary rat cerebellar granule cells.
- To determine the impact of these compounds on cell viability, intracellular calcium and zinc levels, and mitochondrial membrane potential.
Main Methods:
- Primary cultures of rat cerebellar granule cells were exposed to Thimerosal (TH) with or without serum proteins, albumin, l-cysteine (Cys), d,l-homocysteine (Hcy), N-acetyl cysteine (NAC), l-methionine (Met), or glutathione (GSH).
- Cell viability, intracellular calcium and zinc concentrations, and mitochondrial membrane potential were measured.
- (1)H NMR spectroscopy was used to monitor the interaction between TH and thiols.
Main Results:
- Thimerosal (TH) significantly decreased cell viability, which was partially prevented by serum proteins and dose-dependently by Cys, Hcy, NAC, and GSH (but not Met).
- TH-induced increases in intracellular calcium and zinc, and decreased mitochondrial membrane potential were abolished by sulfur-containing compounds (except Met) at 600 μM.
- Extracellular interaction of TH with thiols was observed, suggesting a mechanism for neuroprotection and potential redistribution of ethylmercury.
Conclusions:
- Proteins and sulfur-containing amino acids (Cys, Hcy, NAC, GSH) individually reduce Thimerosal (TH) neurotoxicity in cerebellar granule cells.
- These compounds protect neurons by interacting with the ethylmercury moiety of TH, preventing cellular damage.
- The combination of proteins and sulfur-containing compounds exhibits a complex modulation of neuronal survival in the presence of TH.
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