T. Shibasaki et al., EFFECT OF TRIETHYLENEPENTAMINEHEXAACETIC ACID ON THE RENAL DAMAGE IN CADMIUM-TREATED SYRIAN-HAMSTERS, Biological trace element research, 50(2), 1995, pp. 157-165
Cadmium (Cd)-induced nephropathy was treated by triethylene-pentamineh
exaacetic acid (TTHA) in male Syrian hamsters. Hamsters injected three
times a week with 3 mg/kg body wt CdCl2 showed proteinuria, urinary N
-acetyl-beta-D-inglucosaminidase (NAG), and fractional excretion of so
dium (FENa) when compared to saline-injected control. Cd-treated hamst
ers injected ip with TTHA 10 mg/kg body wt five times a week showed re
duction of renal damage, including reductions in urinary protein (from
6.7 +/- 2.2 to 4.3 +/- 0.5 mg/d) and NAG (0.17 +/- 0.06 to 0.04 +/- 0
.02 U/d). Urinary excretion of Cd was significantly increased (from 87
+/- 51.3 to 3052 +/- 1485 mg/L) by TTHA administration. Cd concentrat
ion in renal cortical tissue was slightly reduced (26.4 +/- 3.0 to 21.
8 +/- 2.7 mg/g. protein). Excretion of malondialdehyde (MDA) was incre
ased only in Cd-injected hamsters (to 2.1 +/- 1.6 nM/L), and elevated
MDA in renal cortical tissue was not reduced by the administration of
TTHA (1041 +/- 105 VS 1104 +/- 358 nM/g protein). Glutathione (GSH) co
ncentration in the renal cortex was significantly elevated after Cd ad
ministration and further increased after TTHA administration (5.5 +/-
2.1 to 9.8 +/- 2.0 mu g/50 mg protein). There were no marked effects o
n creatinine clearance (Ccr) and hematocrit. Moreover, renal morpholog
ical changes were improved significantly by treatment with TTHA. We de
monstrated the efficacy of TTHA in the treatment of Cd-induced nephrop
athy in hamsters. Although the precise mechanism of the TTHA effects o
n Cd-induced nephropathy has not been elucidated, it might involve GSH
reducing the elevated MDA concentration in renal tissue.