Chelation of cadmium without increased renal cadmium deposition.
Cadmium (Cd) is mainly accumulated in liver and kidney bound to metallothionein (MT) and excreted very slowly from the body. In chronic exposure, Cd is gradually transported from liver to kidney; the renal toxic effects appear when renal Cd concentration exceeds the critical concentration. In order to prevent the Cd-induced renal disease, it is important to control the movement of Cd to the kidney and its renal deposition. However, the chelation of Cd from liver is difficult because of the high affinity of intracellular MT for Cd. A number of chelating agents containing both carboxyl and thiol groups were able to mobilize and excrete Cd more easily in a short time (1/2 hr) after Cd exposure than longer times (24 hr), after MT synthesis. The renal deposition of Cd increased on BAL (2,3-dimercaptopropanol) treatment a short time (1/2 hr) after Cd exposure. However, it was observed that if BAL was administered 24 hr after Cd exposure, it could mobilize Cd from hepatic MT and increase the biliary excretion of Cd without any increase in renal Cd concentration. Studies using a number of structurally related thiols (mono-, di- and trithiols) showed that the major structural requirement for in vivo chelation of Cd from intracellular MT were the vicinal thiol groups on an aliphatic chain, and lipophilicity. BAL was the most effective of all the compounds studied and it did not mobilize Cd to the kidney, when most of the intracellular Cd was bound to MT. Furthermore, a delayed treatment with BAL or DTPA (diethylenetriamine pentaacetic acid) after synthesis of MT resulted in an increase in fecal or urinary excretion of Cd in rat model experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001646:Bile / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D004112:Dimercaprol / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008668:Metallothionein / Q000096:biosynthesis / Q000502:physiology; D004369:Pentetic Acid / Q000494:pharmacology
D002614:Chelating Agents; D002104:Cadmium; D004112:Dimercaprol; D004369:Pentetic Acid; D008668:Metallothionein