MECHANISM OF NEPHROTOXICITY INDUCED BY REPEATED ADMINISTRATION OF CADMIUM CHLORIDE IN RATS

To explore the mechanism of Cd nephrotoxicity, CdCl2 was subcutaneousl y injected to rats, at 3 mg Cd/kg body weight once a day, for 8 d. in the liver, Cd bound-to metallothioneins (MTs-Cd) rose from d 1 after t he initiation of CdCl2 administration, and reached a plateau after the administration ceased. In the plasma, MTs-Cd rose from d 4, peaked on d 8, and gradually fell thereafter. In the kidneys, leucine aminopept idase (LAP) and N-acetyl beta-D-glucosaminidase (NAG) fell during d 6- 20, and Cd bound to cellular membranes (Mem-Cd) rose from d 1 and reac hed a plateau during d 6-20. The Mem-Cd levels were significantly corr elated with the reduction in the LAP and NAC activity; the values of M Ts-Cd plus Mem-Cd were almost equivalent to those of total Cd. These f indings showed that the hepatic synthesis of MTs-Cd occurred followed by its release into plasma; the extent of renal injury was aggravated as the plasma level of MTs-Cd rose; and a greater part of the renal Cd distributed intracellularly as the MTs binding form, while the residu al Cd distributed as the cellular membrane-binding form. Also, it was suggested that Cd that occurred as the cellular membrane-binding form in the kidneys was involved in manifestation of renal injury.