N-benzyl-D-glucamine dithiocarbamate and N-p-isopropylbenzyl-D-glucamine dithiocarbamate improve the protective effect of diethyldithiocarbamate against cadmium-induced testicular toxicity in rats.
The protective effects of combined treatment with diethyldithiocarbamate (DED) plus N-benzyl-D-glucamine dithiocarbamate (BGD) or DED plus N-p-isopropylbenzyl-D-glucamine dithiocarbamate (PBGD) against the testicular toxicity caused by acute exposure to cadmium (Cd) in rats were studied. Rats were injected subcutaneously with 109CdCl2 (3 mg Cd and 74 kBq of 109Cd/kg) and 30 min later, they were injected intraperitoneally with the chelating agents (1 mmol/kg each). Cd injection increased lipid peroxidation and concentrations of hemoglobin, Ca and Fe in the testes, decreased the testicular weight and nonprotein SH (NP-SH), and caused sterility. The coadministration of DED with BGD or PBGD significantly prevented the increase in the lipid peroxidation, hemoglobin, Ca and Fe in the testes, the decrease in the testicular weight and NP-SH, and the sterility caused by Cd injection. DED plus BGD or DED plus PBGD significantly decreased the Cd concentration in the testes without the redistribution of Cd to the brain and kidney, which is observed following treatment with DED alone. The coadministration of DED plus BGD or DED plus PBGD significantly increased the blood Cd concentration and the Cd distribution in the red blood cells compared to Cd alone. These results indicate that the coadministration of BGD or PBGD with DED prevents the accumulation of Cd in the testes on the basis of greater blood distribution of Cd, which results from the uptake of Cd by the red blood cells, without the redistribution of Cd to the brain, resulting in an improvement of the protective effect of DED against the Cd-induced testicular toxicity.
Kojima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Sugimura
Y
Y
Ono
H
H
Shimada
H
H
Funakoshi
T
T
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002106:Cadmium Radioisotopes; D002614:Chelating Agents / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D005298:Fertility / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013733:Testicular Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000494:pharmacology*
D002106:Cadmium Radioisotopes; D002614:Chelating Agents; D006454:Hemoglobins; D011506:Proteins; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D002104:Cadmium; C076771:N-4-isopropylbenzylglucamine dithiocarbamate; D013012:Sorbitol; D004050:Ditiocarb; C048763:N-benzylglucamine dithiocarbamate