Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte cultures.
The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and intracellular lipid peroxidation and active oxygen species. Primary hepatocyte cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of 109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused by all Cd exposure concentrations were significantly prevented by treatment with BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure for 30 min significantly prevented increases in extracellular LDH activity. Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4 h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h, respectively. Moreover, the increases in the level of active oxygen species caused by Cd exposure for 30 min were significantly prevented by treatment with the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the protective effects of chelating agents presumably result from a decrease in the Cd level, the effective sequestration of the reactive Cd ion, and the direct preventive effect on the active oxygen species in the hepatocytes.
Funakoshi
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Japan.
Ueda
K
K
Shimada
H
H
Kojima
S
S
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000517:prevention & control; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D004347:Drug Interactions; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use
D002614:Chelating Agents; D013859:Thiocarbamates; D002104:Cadmium; C068198:N-4-hydroxymethylbenzylglucamine dithiocarbamate; D013012:Sorbitol; D007770:L-Lactate Dehydrogenase; C048763:N-benzylglucamine dithiocarbamate