Indications for the presence of circulating peroxidized low density lipoproteins in WHHL rabbits treated with antioxidants.
Low density apolipoprotein (apo) B-100 in homozygous WHHL rabbits appears heterogeneous on SDS-PAGE. At least four high molecular weight apolipoproteins were identified in contrast to the uniform apo B-100 band in the very low density lipoprotein (VLDL) fraction of WHHL-homozygotes and the apo B containing lipoproteins present in WHHL heterozygotes or New Zealand White rabbits. We studied whether these aberrations in homozygote WHHL-LDL were due to physical changes induced by lipid peroxidation. Therefore we treated WHHL rabbits for 28 days with a standard dose of 1% probucol or with a dose of 0.1% vitamin E and studied the parameters indicating lipid peroxidation in circulating LDL and in vitro in relation to its antioxidant content. The LDL of probucol-fed rabbits appeared completely resistant against oxidation in vitro with Cu2+ ions. LDL fluorescence and serum malondialdehyde concentrations, indicators of lipid peroxidized LDL, were lower than in the control WHHL rabbits. LDL of vitamin E-fed WHHL rabbits showed a twofold increased lag phase in comparison with LDL of control-fed animals; the maximal rate of oxidation was 2- to 3-fold lower while LDL fluorescence was between the values obtained in the two other groups. Malondialdehyde concentration in the vitamin E-treated group was also decreased when compared with controls. Despite these indications of increased lipid peroxidized circulating LDL in WHHL controls which could be reversed, at least partially, by the antioxidant treatments applied, these treatments were without effect on the physical structure of LDL as examined with agarose gel electrophoresis. Neither antioxidant treatment changed the typical apo B-100 pattern in WHHL-LDL.
Demacker
P N
PN
Department of General Internal Medicine, University Hospital Nijmegen, The Netherlands.
Hijmans
A G
AG
Kleinveld
H A
HA
Stalenhoef
A F
AF
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D008970:Molecular Weight; D011341:Probucol / Q000627:therapeutic use; D011817:Rabbits; D014810:Vitamin E / Q000378:metabolism / Q000627:therapeutic use
D000975:Antioxidants; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008055:Lipids; D008077:Lipoproteins, LDL; D014810:Vitamin E; D008315:Malondialdehyde; D011341:Probucol