Disposition in rat of [2-3H]-trans-4-hydroxy-2,3-nonenal, a product of lipid peroxidation.
1. 4-Hydroxy-2,3-nonenal (HNE) is an end product of lipid peroxidation (LPO) and a well known cytotoxic aldehyde that exhibits a variety of biological effects. In this study the in vivo disposition and covalent binding of i.p. administered [2-3H]HNE was examined in the rat. 2. It was found that several metabolites of [2-3H]HNE are excreted in urine among which at least four mercapturic acids. 1,4-Dihydroxynonane mercapturic acid (DHN-MA) appeared to be the most abundant mercapturic acid excreted in urine (3.5% of the dose) and the excretion of the other three mercapturic acids amounted to 2% of the dose. 3. Within 48 h following i.p. administration of 5 or 25 mumol/kg bodyweight [2-3H]HNE (specific activity 4 microCi/mumol) about 25% of the radioactivity was excreted in urine, whereas 18% of the radioactivity appeared in the faeces. 4. After 48 h, 7% of the radioactivity was still present in the liver and 0.2% in other organs, but this radioactivity appeared to not to be covalently bound to cellular macromolecules. It was found that only 0.13% of the radioactivity was covalently bound in the liver and even less in other organs.
de Zwart
L L
LL
Leiden/Amsterdam Center for Drug Research, Free University, Department of Pharmacochemistry, The Netherlands.
Hermanns
R C
RC
Meerman
J H
JH
Commandeur
J N
JN
Vermeulen
N P
NP
D000447:Aldehydes / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D005243:Feces; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014316:Tritium
D000447:Aldehydes; D014316:Tritium; C027576:4-hydroxy-2-nonenal