Photophysical and photobiological behavior of antimalarial drugs in aqueous solutions.

This article describes the results of a combined photophysical and photobiological study aimed at understanding the phototoxicity mechanism of the antimalarial drugs quinine (Q), quinacrine (QC) and mefloquine (MQ). Photophysical experiments were carried out in aqueous solutions by stationary and time-resolved fluorimetry and by laser flash photolysis to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed on irradiation. The results obtained showed that fluorescence and intersystem crossing account for all the adsorbed quanta for Q and MQ (quantum yield of about 0.1 and 0.9, respectively) and only for 24% in the case of QC, which has a negligible fluorescence quantum yield (0.001). Laser flash photolysis experiments evidenced, for QC and MQ, the occurrence of photoionization processes leading to the formation of the radical cations of the drugs. The effects of tryptophan and histidine on the excited states and transient species of the three drugs were also investigated. In parallel, the photoactivity of the antimalarial drugs was investigated under UV irradiation on various biological targets through a series of in vitro assays in the presence and in the absence of oxygen. Phototoxicity on 3T3 cultured fibroblasts and lipid photoperoxidation were observed for all the drugs. The photodamage produced by the drugs was also evaluated on proteins by measuring the photosensitized cross-linking of spectrin. The combined approaches were proven to be useful for understanding the mechanism of phototoxicity induced by the antimalarial drugs.

Cell attachment to extracellular matrices is modulated by pulsed radiation at 820 nm and chemicals that modify the activity of enzymes in the plasma membrane.

BACKGROUND AND OBJECTIVES: Adhesive interactions between cells and extracellular matrices play a regulative role in wound repair processes. The objective of this investigation is to study action mechanisms of pulsed radiation at 820 nm on cellular adhesion in vitro. Light emitting diodes (LED) at 820 nm are widely used for treatment of wounds of various etiology. STUDY DESIGN/MATERIALS AND METHODS: The LED (820 +/- 10 nm, 10 Hz, 16-120 J/m(2)) is used for the irradiation of HeLa cell suspension. In parallel experiments, amiloride (5 x 10(-4) M), ouabain (7 x 10(-5) M, 7 x 10(-4) M), quinacrine (6 x 10(-4) M), arachidonic acid (1 x 10(-5) M), glucose (2 x 10(-4) M), and ATP (5 x 10(-5) M) are added to the cell suspension before or after the irradiation procedure. The cell-glass adhesion is studied using the adhesion assay technique described in Lasers Surg Med 1996; 18:171. RESULTS: Cell-glass adhesion increases in a dose-dependent manner following the irradiation. Preirradiation eliminates the inhibition of cell attachment caused by ouabain, arachidonic acid, and ATP. The inhibitive effect of quinacrine on the cell attachment is eliminated by the irradiation performed after the treatment with the chemical. Irradiation and amiloride have a synergetic stimulative effect on the cell attachment. The threshold dose for the cell attachment stimulation by the irradiation is decreased by the treatment of the cell suspension with amiloride or ouabain. CONCLUSIONS: The results obtained indicate that pulsed IR radiation at 820 nm increases the cell-matrix attachment. It is the modulation of the monovalent ion fluxes through the plasma membrane and not the release of arachidonic acid that is involved in the cellular signaling pathways activated by irradiation at 820 nm. Preirradiation has a protective effect against the inhibitive action of ouabain, arachidonic acid, ATP, and quinacrine on cell attachment process. It is supposed that irradiation activates those signaling pathways in cells which attenuate the inhibitive action of these chemicals.

The action of ionizing radiation on DNA in the presence of quinacrine. III. E.S.R. study: spin transfer in gamma-irradiated lyophilized DNA-quinacrine complexes.

E.S.R. spectra of different DNA-quinacrine complexes show as well at 77 K as at 293 K that there exists an electron transfer from the bases to quinacrine facilitated by the overlap of the theta-orbitals of the bases and the intercalated dye. The transfer range may extend over more than 25 or 50 nucleotides depending on the intercalation model considered.

The action of ionizing radiation on DNA in the presence of quinacrine. I. UV absorption and fluorescence measurements.

It is shown by UV absorption and absolute fluorescence spectroscopy of solutions containing both DNA and quinacrine that the components experience mutual radio-protection due to scavenging of water radicals. From measurements at different ionic strengths it is inferred that quinacrine bound to DNA is more efficiently protected than the free compound. Furthermore, release of bound quinacrine from DNA is observed at higher doses.