Prediction of uptake of methyl mercury by rat erythrocytes using a two-compartment model.
The uptake of methyl mercury (MeHg) by isolated rat erythrocytes was studied at 37 degrees C using MeHg-cysteine (MeHgCySH), MeHg-glutathione (MeHgGSH), MeHg-mercaptalbumin (MeHgMASH) and the mixture of MeHgCySH with MeHgGSH, MeHgCySH with MeHgMASH, MeHgGSH with MeHgMASH at different MeHg concentrations. The measured MeHg concentrations were analyzed according to the Akaike's information criterion in order to determine the suitable compartment model. After determining a two-compartment model, a model-independent two-compartment model was developed from the kinetics of uptake of MeHg at a concentration of 1 mmol MeHg/l packed erythrocytes using MeHgCySH, MeHgGSH and MeHgMASH, respectively. The developed two-compartment model was validated by predicting the kinetics of uptake of MeHg by rat erythrocytes at different MeHg concentrations and different mixtures of MeHg-complexes. Then, the predicted values were compared with the measured values. The results suggested: 1) MeHg uptake appeared suitable to be described by a two-compartment model, while using MeHgGSH, MeHgMASH, MeHgCySH at lower concentrations and the mixtures of MeHg-complexes; 2) MeHgCySH uptake was slowest among three kinds of MeHg-complexes, although a postulated cysteine-facilitated MeHgCySH transport system might exist in erythrocyte membrane; 3) the mixture of MeHg-complexes might facilitate MeHgCySH uptake; 4) there might be a second MeHg intracellular compartment in rat erythrocytes.
Wu
G
G
Biochemical Section, National Institute for Minamata Disease, Kumamoto, Japan.
D000818:Animals; D002451:Cell Compartmentation; D003545:Cysteine / Q000097:blood / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005978:Glutathione / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008767:Methylmercury Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D008954:Models, Biological; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000493:pharmacokinetics
D008767:Methylmercury Compounds; D012709:Serum Albumin; C001702:mercaptoalbumin; D005978:Glutathione; D003545:Cysteine