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.
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.
Toyokuni
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Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Japan.
Luo
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XP
Tanaka
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Uchida
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Hiai
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Lehotay
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D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002849:Chromatography, Gas; D005233:Fatty Alcohols / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D002273:Carcinogens; D005233:Fatty Alcohols; D005290:Ferric Compounds; D008315:Malondialdehyde; C011159:acyloin; C027576:4-hydroxy-2-nonenal; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate