Comparison of In Vivo with In Vitro Pharmacokinetics of Mercury Between Methylmercury Chloride and Methylmercury Cysteine Using Rats and Caco2 Cells

Abstract

The in vivo and in vitro pharmacokinetics of mercury (Hg) were compared between methylmercury chloride (MeHg·Cl) and methylmercury cysteine (MeHg-Cys) using rats and Caco2 cells because humans can be exposed to MeHg compounds through dietary fish. The in vivo pharmacokinetics of Hg immediately after the digestion of MeHg compounds are still obscure. In Caco2 cells, membrane uptake and subcellular distribution of MeHg compounds were examined. When rats received it intravenously, MeHg·Cl showed 20-fold greater plasma and 2-fold greater blood concentrations of Hg than MeHg-Cys, indicating that their pharmacokinetic properties are different. One hour later, however, Hg concentrations in plasma and blood became virtually identical between MeHg·Cl and MeHg-Cys, although blood Hg concentrations were >100-fold greater than those in plasma. When administered into the closed rat's jejunum loop, MeHg·Cl and MeHg-Cys were rapidly and efficiently taken up by intestinal membranes, and Hg was retained in intestinal membranes for a relatively long time. When administered orally, no difference was observed in plasma and blood Hg concentrations between MeHg·Cl and MeHg-Cys: plasma and blood Hg concentrations increased gradually and reached steady levels at 8 h after administration. In Caco2 cells, uptake of MeHg-Cys was significantly suppressed by L-leucine, although this was not seen with MeHg·Cl. In Caco2 cells, 81 % of Hg was recovered from cytosol fractions and 13 % of Hg from nuclear fractions (including debris) after a 2-h incubation with MeHg-Cys. In conclusion, the mechanism of membrane uptake and volume of distribution in the initial distribution phase were clearly different between MeHg·Cl and MeHg-Cys. However, such pharmacokinetic differences between them disappeared 1 h after intravenous and after oral routes of administration, possibly due to the metabolism in the body.

Increased methylmercury toxicity related to obesity in diabetic KK‐Ay mice

“…CD204-positive macrophages were observed in the spleen of MeHg-exposed KK-Ay mice, indicating cellular injury of the spleen. It is known that MeHg in the blood stream is rapidly incorporated into erythrocytes in MeHg-administered animals (Mori et al, 2012). The dysfunction of the spleen may be involved in the clearance of erythrocytes containing mercury.…”

What are the toxicological effects of mercury in Arctic biota?

“…More than 95% of the methylmercury (MeHg) in food items is taken up by mammals, whereas the corresponding proportion for inorganic Hg is thought to be lower than 15% (Berlin, 1986;WHO, 1993;Mori et al, 2012). Methylmercury is transported through the intestinal mucosa, and lymph and blood vascular portal systems transport it into the organs where it may be demethylated, stored, or excreted.…”

Protection of Endogenous Thiols against Methylmercury with Benzimidazole‐Based Thione by Unusual Ligand‐Exchange Reactions

“…The high toxicity of MeHg + is mainly due to its strong affinity towards endogenous thiols, such as l ‐cysteine ( l ‐CysH) and glutathione (GSH), and thiol‐ or selenol‐containing proteins found in biological systems . The toxicity of MeHg + varies according to its chemical form and exposure amount . MeHg + binds with cysteine residue to form a MeHgCys complex that can easily cross cellular membranes through a transporter, called LAT1, and thereby it acts as a driving force in transporting toxic MeHg + into various tissues .…”