Photohemolysis Sensitized by the Furocoumarin Derivative Alloimperatorin and its Hydroperoxide Photooxidation Product.

The dark and photosensitized effects of alloimperatorin methyl ether 1 (hereafter simply alloimperatorin) and its photooxygenation product alloimperatorin hydroperoxide 2 were investigated on human erythrocytes. The results reveal that the furocoumarin 1 photosensitizes efficiently the hemolysis of erythrocytes. The rate of photohemolysis increases on raising the temperature of the postirradiated incubation from 4°C to 37°C.

Systemic suppression of the contact hypersensitivity by the products of protoporphyrin IX photooxidation.

Photodynamic therapy (PDT) is frequently accompanied by induction of systemic immunosuppression. Photochemical mechanisms underlying this effect are not completely understood. Here, we demonstrate the immunosuppressive activity of photooxidation products of protoporphyrin IX dimethyl ester (PPIX) in a murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB).

Modulation of delayed type hypersensitivity in mice treated with photoproducts of various photosensitizers used in photodynamic therapy.

Photodynamic therapy is frequently accompanied by the induction of immunosuppression. The photochemical mechanisms behind the induction of this immunosuppression are not clear. The purpose of this study was to evaluate the potential of photoproducts of merocyanine 540 (MC540), protoporphyrin IX (PPIX) and hematoporphyrin derivative (HpD) to cause modulation (suppression/activation) of the T cell immune response in vivo.

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.

The application of antioxidants in investigations and optimization of photochemotherapy.

Psoralens (furocoumarins) are photosensitizers of plant origin. They are used in combination with near-ultraviolet (320-400 nm) light for the treatment of vitiligo, psoriasis, cutaneous T-cell lymphoma (CTCL), alopecia areata, eczema, and other skin diseases. Photobiological effects of psoralens in humans are numerous.

Suppression of delayed-type hypersensitivity and hemolysis induced by previously photooxidized psoralen: effect of fluence rate and psoralen concentration.

The kinetics of the formation of biologically active psoralen photooxidation (POP) products were analyzed by the biological effects produced. Effects of the UV light fluence rate and psoralen concentration during the preirradiation were investigated to assess the yield of POP products, which were active in vivo (inducing suppression of delayed-type hypersensitivity [DTH] reaction to sheep red blood cells) and in vitro (altering the human erythrocyte membrane permeability). It was shown that the reciprocity law of the irradiation fluence rate and time was not valid in the case of POP-induced hemolysis and DTH suppression.

The Attenuation of Effectors and Induction of Suppressors of Delayed Type Hypersensitivity Reaction under the Treatment with Psoralen Photooxidation Products.

Psoralens, together with ultraviolet light A (PUVA), are used for the treatment of the series of T cell mediated diseases. The role of photooxidative reactions in psoralen phototherapy is not entirely clear. Using model of delayed type hypersensitivity (DTH) reaction to sheep red blood cells and evaluating the antibody production in mice, we investigated the influence of produced in vitro psoralen photooxidation products (POP) on the functions of T and B effectors.

Products of psoralen photooxidation possess immunomodulative and antileukemic effects.

It has been proposed that the therapeutic effect of PUVA (psoralens+UVA radiation) is connected to its immunomodulative properties, and that the molecular basis of such properties is the oxygen-independent photoaddition of psoralens to DNA. We have investigated effects of preliminary photooxidized psoralens (POP) on the delayed-type hypersensitivity reaction (DTH) to sheep red blood cells and on growth of grafted T-cell lymphoma EL-4 in mice. We have shown that intravenous injection of POP at low concentrations activated, and at high concentrations suppressed, DTH.

Psoralen-photosensitized damage of rat peritoneal exudate cells.

Psoralen-sensitized photodamage (PUVA) of rat peritoneal exudate cells was investigated. Quartz-activated luminol-dependent chemiluminescence (ChL) was registered and the amount of trypan-positive cells was determined. Irradiation of peritoneal exudate cells in the presence of psoralen resulted in a dose-dependent monotonous inhibition of ChL.