Related Experiment Videos
Peroxynitrite-modified 99mTc-beta-VLDL: tissue distribution and plasma clearance rate
E L Silva1, J C Meneghetti, I J Coelho
1Department of Clinical and Toxicological Analysis, University São Paulo, São Paulo, Brazil.
Free Radical Biology & Medicine
|August 11, 2001
Summary
Peroxynitrite modifies beta-very-low-density lipoprotein (beta-VLDL), causing faster plasma clearance and increased tissue accumulation, particularly in the liver and kidneys. This modification is significant in hypercholesterolemia.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Oxidative Stress
Background:
- Free radicals like superoxide and nitric oxide generate peroxynitrite, a potent oxidant.
- Peroxynitrite modifies lipoproteins, increasing their atherogenic potential.
Purpose of the Study:
- To investigate the impact of peroxynitrite modification on beta-very-low-density lipoprotein (beta-VLDL).
- To assess the biodistribution, plasma clearance, and cellular uptake of modified beta-VLDL.
Main Methods:
- Peroxynitrite-modified beta-VLDL (99mTc-per-beta-VLDL) and native beta-VLDL (99mTc-nat-beta-VLDL) were injected into normocholesterolemic and hypercholesterolemic rabbits.
- In vivo biodistribution and plasma clearance rates were measured.
- In vitro uptake by THP-1 cells was analyzed.
Main Results:
- Peroxynitrite-modified beta-VLDL exhibited faster plasma clearance than native beta-VLDL in both rabbit groups.
- Tissue accumulation, per gram, followed the order: kidney > liver > spleen > adrenal gland > lung > aorta > heart > muscle.
- THP-1 cell uptake of modified beta-VLDL was significantly higher than native beta-VLDL.
Conclusions:
- Peroxynitrite-modified beta-VLDL is rapidly cleared from plasma and accumulates in key tissues, notably the liver and kidneys.
- These findings are crucial for understanding lipoprotein accumulation in hypercholesterolemic conditions.
- Peroxynitrite-induced lipoprotein modification may exacerbate atherosclerosis.