EFFICACY OF AMPHIPATHIC DITHIOCARBAMATES IN INTRACELLULAR CADMIUM MOBILIZATION AND IN MODULATION OF HEPATIC AND RENAL METALLOTHIONEIN IN CADMIUM PREEXPOSED RAT

Forty-eight hours after an intraperitoneal injection of cadmium chlori de (1.5 mg Cd/kg) to female albino rats, Cd was mainly localized in th e hepatic and renal supernatant cytosolic fraction (SCF). Seventy-two hours later, the total hepatic burden remained unchanged but the total renal burden was enhanced, showing its tendency to accumulate in the kidney. A single dose (0.4 mmol/kg, i.p.) of sodium N-benzyl-D-glucami ne dithiocarbamate (BG.DTC) or sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeO.BG.DTC), 24 h after Cd injection, efficiently mob ilized Cd from hepatic SCF, apparently from cadmium-metallothionein (C d-MT); MeO.BG.DTC also removed Cd from hepatic nuclear mitochondrial f raction. This treatment, however, increased the renal burden of Cd, in dicating that the chelating agents, at least partly, transport Cd from the liver and possibly from other sites into the kidney. Three doses of the chelators further enhanced mobilization of Cd from hepatic as w ell as renal SCF, as corroborated by its enhanced urinary and, to a gr eater extent, fecal excretion. Hepatic and renal MT were induced sever al-fold above normal after a single dose of Cd as well as single or re peated doses of BG.DTC or MeO.BG.DTC. Seventy-two hours after a Cd inj ection, the hepatic MT declined to half of the induced level while the renal MT remained elevated. Administration of BG.DTC or MeO.BG.DTC in Cd pre-treated rats produced an additive response in hepatic MT, but the response in renal MT was less than additive at one dose and slight ly declined after three doses. Hepatic Zn and Cu and renal Zn increase d on treatment with Cd but were depleted after a single or repeated in jection of BG.DTC or MeO.BG.DTC in normal as well as in Cd pre-exposed animals. The results indicate that intracellular access of amphipathi c dithiocarbamates effectively mobilizes MT-bound Cd, which is prefere ntially excreted in the feces, and helps avoid further burden on the k idney and consequent nephrotoxicity. Additionally, MeO.BG.DTC was a be tter inducer of hepatic MT to help increased capture of toxic metal fr om the initial circulation and consequent toxicity. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.