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Published on: January 8, 2016
Methylmercury-cysteinylglycine constitutes the main form of methylmercury in rat bile
1Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Abstract:
The chemical form of methylmercury (MM) in bile was studied by gel filtration and ion exchange chromatography using male rats of various ages. EDTA was added to all mixtures used throughout the experimental procedures in order to prevent oxidation of non-protein sulfhydryl compounds (NPSHs). MM-cysteinylglycine (CysGly) was found to be a predominant chemical form of MM in bile of 4 to 22-week-old rat exposed to methylmercuric chloride. The ratio of MM-glutathione (GSH) tended to increase with age after 4 weeks until 12 weeks of age, reflecting the age-dependent increase in the ratio of GSH to total NPSHs in bile. In 8-week-old rats, although the biliary concentration of GSH was about three times higher than that of CysGly, MM-CysGly was still one of the main chemical forms of MM in bile. This suggests that CysGly has a higher affinity for MM than GSH. In fact, when MM was mixed in vitro with GSH and CysGly in the same molar ratio as that in the bile of 8-week-old rat, MM-CysGly was found to be a predominant mercury-thiol complex. Thus, age-dependent changes in the molar ratio of biliary NPSHs together with their affinity to MM seems to determine the biliary chemical form of MM administered or added into the bile in vitro.
Insights
Methylmercury (MM) in rat bile primarily binds to cysteinylglycine (CysGly), even when glutathione (GSH) is more abundant. This indicates CysGly
Area of Science:
- Biochemistry
- Toxicology
- Environmental Health
Background:
- Methylmercury (MM) is a potent neurotoxin.
- The chemical form of MM influences its toxicity and excretion.
- Bile is a key route for MM elimination.
Purpose of the Study:
- To investigate the chemical forms of methylmercury (MM) in rat bile.
- To determine the influence of age and non-protein sulfhydryl compounds (NPSHs) on MM binding.
- To elucidate the binding affinity of MM to biliary thiols.
Main Methods:
- Gel filtration and ion exchange chromatography were used to analyze MM in rat bile.
- EDTA was employed to prevent oxidation of NPSHs.
- In vitro experiments assessed MM binding to glutathione (GSH) and cysteinylglycine (CysGly).
Main Results:
- Methylmercury-cysteinylglycine (MM-CysGly) was the predominant form in rat bile across various ages.
- The ratio of methylmercury-glutathione (MM-GSH) increased with age, correlating with elevated GSH levels.
- In vitro, MM-CysGly formed preferentially over MM-GSH, suggesting higher affinity of CysGly for MM.
Conclusions:
- Cysteinylglycine (CysGly) exhibits a higher affinity for methylmercury (MM) than glutathione (GSH).
- Age-dependent changes in biliary non-protein sulfhydryl compounds (NPSHs) and their affinities dictate the chemical form of MM in bile.
- Understanding these interactions is crucial for predicting MM toxicity and developing detoxification strategies.
