DISPOSITION IN RAT OF [2-H-3]-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-H-3]HNE was examined in the rat. 2. I t was found that several metabolites of [2-H-3]HNE are excreted in uri ne among which at least four mercapturic acids. 1,4-Dihydroxynonane me rcapturic acid (DHN-MA) appeared to be the most abundant mercapturic a cid excreted in urine (3.5 % of the dose) and the excretion of the oth er three mercapturic acids amounted to 2 % of the dose. 3. Within 48 h following i.p. administration of 5 or 25 mu mol/kg bodyweight [2-H-3] HNE (specific activity 4 mu Ci/mu mol) 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 appeare d not to be covalently bound to cellular macromolecules. It was found that only 0.13 % of the radioactivity was covalently bound in the live r and even less in the other organs.