Photohemolysis sensitized by the furocoumarin imperatorin and its oxyfunctionalized derivatives.
The dark and photosensitized (366 nm) hemolytic effects of imperatorin and its photooxidation products, the hydroperoxides I and II as well as the corresponding alcohol of the hydroperoxide I (imperatorin alcohol), were studied on human erythrocytes. Imperatorin was shown to photosensitize hemolysis, its fluence (D) dependence of the rate of photohemolysis (V) followed the equation V = V0 + aD2 + bD1/2, in which V0 is the dark hemolysis rate and a and b are constants. At fluences below 200 kJ/m2, the main hemolytic contribution derives from the bD1/2 component, which is due to the in situ formation of the imperatorin hydroperoxides, while at fluences higher than 200 kJ/m2, the main contribution corresponds to the aD2 component due to the two-photon damage of cell membranes. Hydroperoxides I and II induce oxyhemoglobin cross-linking, as well as its conversion to methemoglobin and hemichrome. These reactions involve hydroxyl and alkoxy radicals, as the hemolysis and oxyhemoglobin conversion could be inhibited by t-butanol and butylated hydrotoluene. For comparison, the dark hemolytic effect of the imperatorin alcohol was approximately 10-fold less than of the hydroperoxides.
Potapenko AYa
Department of Medical and Biological Physics, Russian State Medical University, Moscow, Russia. potap@hotmail.com
Kyagova
A A
AA
Andina
E S
ES
Zhuravel
N N
NN
Lysenko
E P
EP
Möller
M
M
Stopper
H
H
Adam
W
W
Saha-Möller
C R
CR
D003624:Darkness; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000187:drug effects / Q000378:metabolism; D018462:Photobiology
D011564:Furocoumarins; D010108:Oxyhemoglobins; C031534:imperatorin