KINETICS AND UPTAKE IN-VIVO OF OXIDATIVELY MODIFIED LYMPH CHYLOMICRONS

The metabolism of oxidized chylomicrons (ox-CMs) was investigated in vivo. CMs from rats fed corn, linseed, or fish oil were oxidized by incubation with 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH) or sodium hypochlorite (NaOCl). Oxidized CMs had a rapid phase of clearance, followed by a slow phase. Clearance of ox-CMs was decreased for corn oil but increased for linseed and fish oil particles. Differences in rates of uptake between CM types or treatment were independent of the rate of remnant formation, but were instead a consequence of decreased clearance. A greater triglyceride-to-cholesteryl ester ratio in liver suggested that there was less lipolysis of ox-CM triglyceride prior to uptake. Hepatic uptake of ox-CMs was decreased, whereas there was increased uptake in spleen. However, the uptake by Kupffer cells of ox-CMs was 43% of total liver uptake after AAPH treatment and 59% after NaOCl treatment, compared with 21% for control CMs. Collectively, our data show that oxidation can have differential effects on the rate of clearance of CMs and that ox-CMs are preferentially cleared by the reticuloendothelial system.