Peroxynitrite-modified (TC)-T-99m-beta-VLDL: Tissue distribution and plasma clearance rate

Free radicals superoxide (O-2(-)) and nitric oxide ((NO)-N-.) are generated by blood vessels and can rapidly react to produce a peroxynitrite anion (O NOO-), a powerful oxidant that modifies lipoproteins making them more ather ogenic. The aim of this study was to investigate the effect of peroxynitrit e-induced modifications on beta -very-low-density lipoprotein (beta -VLDL) as to its biodistribution and plasma clearance rate, as well as the uptake of these particles by THP-1 cells. After being injected into New Zealand Wh ite rabbits, the peroxynitrite-modified beta -VLDL (Tc-99m-per-beta -VLDL) was cleared from circulation faster than the native beta -VLDL (Tc-99m-nat- beta -VLDL) in both normocholesterolemic rabbits (NC) and in hypercholester olemic rabbits (HQ. In HC rabbits, the fractional clearance of Tc-99m-label ed beta -VLDL was significantly lower than in NC rabbits. The in vivo studi es showed that accumulation of Tc-99m-labeled beta -VLDL, expressed per gra m of tissue, followed the decreasing order: kidney > liver > spleen > adren al gland lung > aortic arch > heart ! abdominal aorta > thoracic aorta > ps oas muscle. The high accumulation in the kidneys suggests the processing of 99mTc-labeled apolipoproteins by receptors present in kidney cells. The ac cumulation of Tc-99m-nat-beta -VLDL in the whole organ was the following: l iver > kidney > heart > spleen > adrenal gland > aorta in HC and NC rabbits . The uptake of Tc-99m-per-beta -VLDL by the spleen was greater than the up take by the heart in both groups. The in vitro studies showed that the upta ke of Tc-99m-per-beta -VLDL by THP-1 cells was higher than that of Tc-99m-n at-beta -VLDL. These results show that peroxynitrite-modified beta -VLDL is rapidly removed from plasma and accumulates in several tissues, mainly in the liver and kidney. This may be particularly important in hypercholestero lemic situations that could favor the accumulation of native and peroxynitr ite-modified beta -VLDL in several tissues. (C) 2001 Elsevier Science Inc.