Molecular mechanism of drug photosensitization. Part 6. Photohaemolysis sensitized by tolmetin.
The photosensitizing properties of tolmetin, 5-(p-toluoyl)-1-methyl-2-pyrrolyacetic acid (TLM), have been studied in vitro following the lysis of erythrocytes in phosphate buffer suspensions irradiated with UVA light in the presence of the drug. It was found that the phototoxic properties of the drug are negligible in nitrogen and significant in aerated medium, but that they decrease in oxygen-saturated solution. The investigation of the drug photolysis showed that TLM undergoes photodecarboxylation to p-tolyl 1,2-dimethyl-5-pyrrolyl ketone in nitrogen and to p-tolyl 1-methyl-2-hydroxymethyl-5-pyrrolyl ketone and 5-(p-toluoyl)-1-methyl-2-pyrrole carbaldehyde in air. These photoproducts also undergo photodegradation. The comparison between the photohaemolysis and photolysis results and the effect of suitable additives such as sodium azide, mannitol, butylated hydroxy-anisole, reduced glutathione, superoxide dismutase and copper (II) suggest that the phototoxicity of TLM can be attributed essentially to singlet oxygen in the first step and to its photoproducts when they accumulate and compete with the starting drug in light absorption. Their phototoxic effect is much higher with respect to that of TLM, as shown by comparison of the doses needed to attain 50% photohaemolysis.
D000332:Aerobiosis; D000693:Anaerobiosis; D001386:Azides; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects*; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D007454:Iodides; D015394:Molecular Structure; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D019810:Sodium Azide; D013482:Superoxide Dismutase; D014046:Tolmetin / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
D001386:Azides; D007454:Iodides; D017319:Photosensitizing Agents; D019810:Sodium Azide; D014046:Tolmetin; D013482:Superoxide Dismutase