Jones S G, Holscher M A, Basinger M A, Jones M M
Department of Chemistry, Vanderbilt University, Nashville, TN 37235.
Toxicology. 1988 Dec 16;53(1):135-46. doi: 10.1016/0300-483x(88)90242-9.
An examination of the histopathological appearance of the kidneys of mice treated with cadmium chloride (s.c.) and simultaneously given 1 of 3 chelating agents (i.p.) reveals that the extent of nephrotoxicity is greatest when L-cysteine is the chelating agent. When either of 2 dithiocarbamates capable of mobilizing cadmium from its intracellular deposits, i.e. sodium N-methyl-D-glucamine dithiocarbamate (NaG) or sodium N-benzyl-D-glucamine dithiocarbamate (NaB) is used as the chelating agent, no morphological renal damage was evident. Under these same conditions the testes of the mice were protected to the extent of 95% by both of the dithiocarbamates, whereas the protection afforded by the L-cysteine was only about 50%. One factor governing the extent of nephrotoxicity appears to be the stability of the cadmium complexes which are formed and the manner in which this affects their behavior in vivo. Complexes which are preferentially excreted in the bile, cause little or no renal damage.
对经皮下注射氯化镉并同时腹腔注射三种螯合剂之一的小鼠肾脏进行组织病理学检查发现，当L-半胱氨酸作为螯合剂时，肾毒性程度最大。当两种能够从细胞内沉积物中动员镉的二硫代氨基甲酸盐，即N-甲基-D-葡糖胺二硫代甲酸钠（NaG）或N-苄基-D-葡糖胺二硫代甲酸钠（NaB）中的任何一种用作螯合剂时，未发现明显的肾脏形态学损伤。在相同条件下，两种二硫代氨基甲酸盐对小鼠睾丸的保护程度达95%，而L-半胱氨酸提供的保护仅约为50%。决定肾毒性程度的一个因素似乎是所形成的镉络合物的稳定性以及这对其体内行为的影响方式。优先经胆汁排泄的络合物几乎不会造成或不会造成肾脏损伤。
