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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

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, X P Luo, T Tanaka, K Uchida, H Hiai, D C Lehotay

Free Radic Biol Med. 1997;22(6):1019-27.

PMID: 9034241

Abstract:

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis associated with lipid peroxidation and oxidative DNA damage that finally leads to a high incidence of renal cell carcinoma in rodents. In the present study, we investigated what kinds of C(2-12) saturated and unsaturated aldehydes and C(7-12) acyloins, metabolites of saturated aldehydes, are produced in the kidney and liver within 24 h after single i.p. administration of 15 mg Fe/kg of Fe-NTA, or after repeated (1 or 3 wk) i.p. 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 mass spectrometry with ammonia as reagent gas. Most of the aldehydes and all the acyloins measured revealed a significant dose-dependent increase 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 malondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the increase in aldehydes and acyloins 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) and 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3-hydroxynonan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Immunohistochemistry further demonstrated an increased amount of HNE-modified and MDA-modified proteins in the renal proximal tubules after repeated Fe-NTA administration. Some of the aldehydes measured such as HNE and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulation of these aldehydes may play a role in this renal carcinogenesis model.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP557482	trans-2,cis-6-Nonadienal		557-48-2	Price

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