Chelation of cadmium.
The toxicity of cadmium is determined by chelation reactions: in vivo, Cd2+ exists exclusively in coordination complexes with biological ligands, or with administered chelating agents. The Cd2+ ion has some soft character, but it is not a typical soft ion. It has a high degree of polarizability, and its complexes with soft ligands have predominantly covalent bond characteristics. Cd2+ forms the most stable complexes with soft donor atoms (S much greater than N greater than 0). The coordination stereochemistry of Cd2+ is unusually varied, including coordination numbers from 2 to 8. Even though the Cd2+ ion is a d10 ion, disturbed coordination geometries are often seen. Generally, the stability of complexes increases with the number of coordination groups contributed by the ligand; consequently, complexes of Cd2+ with polydentate ligands containing SH groups are very stable. Cd2+ in metallothionein (MT) is coordinated with 4 thiolate groups, and the log stability constant is estimated to 25.5. Complexes between Cd2+ and low molecular weight monodentate or bidentate ligands, e.g., free amino acids (LMW-Cd), seem to exist very briefly, and Cd2+ is rapidly bound to high molecular weight proteins, mainly serum albumin. These complexes (HMW-Cd) are rapidly scavenged from blood, mainly by the liver, and Cd2+ is redistributed to MT. After about 1 day the Cd-MT complex (MT-Cd) almost exclusively accounts for the total retained dose of Cd2+, independent of the route of exposure. MT-Cd is slowly transferred to and accumulated in kidney cortex. The acute toxicity and interorgan distribution of parenterally administered Cd2+ are strongly influenced by preceding MT induction, or decreased capacity for MT synthesis; however, the gastrointestinal (GI) uptake of Cd2+ seems unaffected by preceding MT induction resulting in considerable capacity for Cd2+ chelation in intestinal mucosa, and this finding indicates that endogenous MT is not involved in Cd2+ absorption. The toxicity of parenterally administered Cd2+ is strongly enhanced when administered as complexes with NTA or STPP , but it is much decreased when administered as a complex with EDTA. In chronic oral exposure the toxicity and GI uptake of Cd2+ is not changed when Cd2+ is administered as a complex with the detergent formula chelating agents NTA, EDTA and STPP . The uptake of Cd2+ from ligated intestine in vivo was not affected by administration of Cd2+ as complexes with CYS or GSH, but significantly reduced by complexation with EDTA or BAL. The acute toxicity of orally administered Cd2+ is reduced when Cd2+ is administered as a complex with EDTA.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D002104:Cadmium / Q000378:metabolism* / Q000633:toxicity; D002614:Chelating Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004064:Digestive System / Q000187:drug effects; D006244:Hardness; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000494:pharmacology; D009696:Nucleic Acids / Q000378:metabolism; D011122:Polyphosphates / Q000494:pharmacology; D011485:Protein Binding; D013816:Thermodynamics
D002614:Chelating Agents; D009696:Nucleic Acids; D011122:Polyphosphates; D002104:Cadmium; D009571:Nitrilotriacetic Acid; C005692:triphosphoric acid