Comparison of antioxidant properties of nifedipine and illuminated nifedipine with nitroso spin traps in low density lipoproteins and phosphatidylcholine liposomes.
Illumination nifedipine, a calcium channel blocker, gives a nitroso-compound, 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-dicarboxylic acid dimethyl ester (NTP), which has spin trapping properties. The antioxidant ability of NTP was tested in a model of lipid peroxidation in low density lipoproteins (LDL) and phosphatidylcholine liposomes, and was compared with parent nifedipine and with other nitroso spin traps such as 3,5-dibromo-4-nitrosobenzene-sulfonic acid (BNTB), nitrosobenzene (NTB) and 2-methyl-2-nitrosopropane (MNP). Nifedipine (20-200 mumol/l) did not inhibit lipid peroxidation either in LDL on in liposomes, whereas its photolytical product NTP was found to be very effective at the same concentrations. The average antioxidant potencies of the nitroso spin traps were similar in both models and decreased in the order: NTP > or = BNTB > NTB > or = MNP. As detected by EPR spectroscopy, the studied nitroso compounds formed stable nitroxide radicals in a pseudo-Diels-Alder reaction, as a result of their interaction with unsaturated bonds of lipids in LDL and liposomes. The relative concentrations of thus formed radicals were in the order: NTP >> BNTB >> NTB approximately MNP and were related to their antioxidant properties. Thus it seems that the ability of the nitroso-compounds to form nitroxide radicals with unsaturated lipids may play a role in the antioxidant effect of these compounds.
Ondrias
K
K
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Misík
V
V
Stasko
A
A
Gergel
D
D
Hromadová
M
M
D000975:Antioxidants / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009543:Nifedipine / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D008081:Liposomes; D010713:Phosphatidylcholines; D009543:Nifedipine