Disposition in rat of [2-3H]-trans-4-hydroxy-2,3-nonenal, a product of lipid peroxidation

Abstract

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 μmol/kg bodyweight [2-³H]HNE (specific activity 4 μCi/μmol) 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 not to be covalently bound to cellular macro-molecules. It was found that only 0·13% of the radioactivity was covalently bound in the liver and even less in the other organs.