Jx. Liu et Gf. Nordberg, NEPHROTOXICITIES OF ALUMINUM AND OR CADMIUM-METALLOTHIONEIN IN RATS -CREATININE EXCRETION AND METABOLISM OF SELECTED ESSENTIAL METALS/, Pharmacology & toxicology, 77(2), 1995, pp. 155-160
The effects of exposure to aluminium (Al) and cadmium (Cd) on urinary
creatinine and protein excretion, and the concentrations of calcium, m
agnesium and copper in kidney and urine were studied in 32 male adult
Wistar rats. The animals were divided into 8 groups, groups id, given
a calcium-deficient diet (0.01%, i.e. 0.01 g calcium/100 g diet weight
) and groups 5-8 a calcium-adequate diet (0.9%) for 6 weeks. Single da
ily intraperitoneal injections of AlCl3 (10.8 mg Al/kg body weight, pe
r day) were done on 6 consecutive days to groups 3, 4, 7 and 8 during
the last week of the experiment. One single intraperitoneal injection
of cadmium-metallothionein (Cd-MT, 0.4 mg Cd/kg) was administered 12 h
r before the final Al dose to groups 2, 4, 6, and 8 and the rats were
sacrificed 47 hr after the Cd-MT injection. The rate of creatinine cle
arance was significantly lower in rats injected intraperitoneally with
either Cd-MT or Al, and the concentrations of magnesium and calcium i
n urine were lower in rats administered both Al and Cd-MT as compared
to those in control groups. Histological examination showed that Al wa
s toxic to the kidney tubule cells of rats, however; an adequate suppl
y of calcium in food protected to some extent the renal tubules from A
l toxicity as indicated by a higher creatinine clearance, and there wa
s also less tubule damage as shown by histological examination. The co
pper concentrations in kidney tissue were lower in groups treated with
either Al or Cd-MT. The above results indicate that: (1) Al administe
red by intraperitoneal injection is nephrotoxic in rats; (2) food defi
cient in calcium increases the vulnerability of the kidney to Al-induc
ed toxicity; (3) the decreased creatinine clearance in Cd-MT-injected
rats may explain the low calcium excretion in urine observed in these
rats.