INDUCTION OF A WIDE-RANGE OF C-2-12 ALDEHYDES AND C-7-12 ACYLOINS IN THE KIDNEY OF WISTAR RATS AFTER TREATMENT WITH A RENAL CARCINOGEN, FERRIC NITRILOTRIACETATE
S. Toyokuni et al., INDUCTION OF A WIDE-RANGE OF C-2-12 ALDEHYDES AND C-7-12 ACYLOINS IN THE KIDNEY OF WISTAR RATS AFTER TREATMENT WITH A RENAL CARCINOGEN, FERRIC NITRILOTRIACETATE, Free radical biology & medicine, 22(6), 1997, pp. 1019-1027
An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal prox
imal tubular necrosis associated with lipid peroxidation and oxidative
DNA damage that finally leads to a high incidence of renal cell carci
noma in rodents. In the present study, we investigated what kinds of C
-2-12 saturated and unsaturated aldehydes and C-7-12 acyloins, metabol
ites of saturated aldehydes, are produced in the kidney and liver with
in 24 h after single ip administration of 15 mg Fe/kg of Fe-NTA, or af
ter repeated (1 or 3 wk) ip administration of 5-10 mg Fe/kg of Fe-NTA.
Amounts of twenty one aldehydes and five acyloins were determined by
capillary column gas chromatography-negative-ion chemical ionization m
ass spectrometry with ammonia as reagent gas. Most of the aldehydes an
d all the acyloins measured revealed a significant dose-dependent incr
ease 1 to 3 h after single administration in the kidney, among which 4
-hydroxy-2-nonenal (HNE) showed the highest increase (27.3-fold) and m
alondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg
wet tissue). In the liver, however, the increase in aldehydes and acyl
oins was less prominent. After repeated administration of Fe-NTA, only
9 aldehydes (ethanal; furfural; trans,trans-2,4-heptadienal; nonanal;
trans-2,cis-6-nonadienal; HNE; decanal; trans-4,cis-4-decenal; MDA) a
nd 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3-hydroxyn
onan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Imm
unohistochemistry further demonstrated an increased amount of HNE-modi
fied and MDA-modified proteins in the renal proximal tubules after rep
eated Fe-NTA administration. Some of the aldehydes measured such as HN
E and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulat
ion of these aldehydes may play a role in this renal carcinogenesis mo
del. Copyright (C) 1997 Elsevier Science Inc.