aluminum-tetrasulfophthalocyanine and Hemolysis

Polyphenolic antioxidants protected against Al-phthalocyanine tetrasulfonate-sensitized photohemolysis of human erythrocytes. A quantitative structure-activity relationship has been obtained to describe the protective effects of di- and trihydroxybenzenes: log cI(50) (microM)=(1.8620+/-1.5565)+(3.6366+/-2.8245) E(1)(7) (V)-(0. 4034+/-0.0765) log P (r(2)=0.8367), where cI(50) represents the concentrations of compounds for the 2-fold increase in the lag-phase of hemolysis, E(1)(7) represents the compound single-electron oxidation potential, and P represents the octanol/water partition coefficient. The cI(50) for quercetin and taxifolin were close, and cI(50) for morin, kaempferol and hesperetin were lower than might be predicted by this equation. The protection from hemolysis by azide, a quencher of singlet oxygen ((1)O(2)) was accompanied by increase in cI(50) of polyphenols, indicating that azide and polyphenols competed for the same damaging species, (1)O(2). These findings point out to two factors, determining the protective efficiency of polyphenols against (1)O(2), namely, ease of electron donation and lipophilicity.

Topics: Antioxidants; Dose-Response Relationship, Drug; Drug Interactions; Erythrocytes; Flavonoids; Hemolysis; Humans; Indoles; Kinetics; Organometallic Compounds; Phenols; Photobiology; Polymers; Radiation-Sensitizing Agents; Reactive Oxygen Species; Structure-Activity Relationship

Photohemolysis of erythrocytes in the presence of aluminum phthalocyanine tetrasulfonate as a sensitizer is inhibited by quercetin. D2O (98.5%) stimulated photohemolysis regardless of quercetin presence, suggesting the participation of singlet oxygen in the process. Since it has been shown that this flavonoid reacts with singlet oxygen, the protective effect might be attributed, at least partially, to its competitive reaction with singlet oxygen. At the molecular level, the alterations of membrane proteins that escort the process of photohemolysis, such as cross-linking of spectrin monomers and of other membrane proteins, were selectively inhibited by quercetin. This effect was qualitatively similar to that induced by NaF, suggesting that quercetin may, like NaF, also inhibit type I photooxidations, which contribute to hemolysis. The lipophilicity of quercetin seems to be an essential factor in the inhibition process; rutin, a water-soluble 3-rutinoside of quercetin, had only a negligible protective effect on photohemolysis.

Topics: Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Indoles; Membrane Proteins; Organometallic Compounds; Oxygen; Photochemotherapy; Photolysis; Quercetin; Radiation-Sensitizing Agents; Singlet Oxygen

The phthalocyanines are a new class of photosensitizers with promising properties for use in photodynamic therapy of cancer [E. Ben-Hur and I. Rosenthal (1985) Int. J. Radiat. Biol., 47, 145--147]. The ability of aluminum phthalocyanine tetrasulfonate (AlPCS) to cause membrane damage upon light exposure was tested using photohemolysis of human erythrocytes as an endpoint. AlPCS was found to be quite efficient in causing red blood cell lysis. Photohemolysis dependency on the light fluence had a characteristic sigmoidal shape. The light fluence required for 50% hemolysis was inversely proportional to AlPCS concentration. Neither singlet oxygen nor hydroxyl radicals appear to be involved in the photohemolysis induced by AlPCS. This is inferred from the observation that exposure of erythrocytes in the presence of D2O or glycerol did not affect the light fluence response curve. These data suggest that photosensitization by AlPCS can cause membrane damage and that this damage may be responsible for cell killing.

Topics: Erythrocyte Membrane; Hemolysis; Humans; Indoles; Organometallic Compounds; Photochemistry; Radiation-Sensitizing Agents