J. Sudo et al., MECHANISM OF NEPHROTOXICITY INDUCED BY REPEATED ADMINISTRATION OF CADMIUM CHLORIDE IN RATS, Journal of toxicology and environmental health, 48(4), 1996, pp. 333-348
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.