Photosensitization by drugs

Abstract

Certain drugs are known to elicit photosensitivity side effects. A satisfactory understanding of the involved mechanistic aspects is necessary to anticipate the photosensitizing potential. We have used tiaprofenic acid (TPA), a photosensitizing nonsteroidal antiinflammatory drug, to illustrate the methodology followed to address this problem. After studying the photophysical and photochemical properties of TPA, the attention has been directed towards the reactivity of its lowest lying π−π* triplet with biomolecules. Photosensitized lipid peroxidation occurs by a mixed type I (radicals) and type II (singlet oxygen) mechanism. In the case of proteins, the photosensitized reactions include Tyr, Trp, and His photodegradation, protein-protein photocrosslinking and drug-protein photobinding. This involves direct quenching of the drug triplet by the amino acid residues (Tyr and Trp) or by oxygen, followed by singlet oxygen oxidation (His and Trp). With DNA, the studies have included comet assay, induction of single-strand breaks in supercoiled DNA, and reaction with 2'-deoxyguanosine and thymidine. Product studies, together with time-resolved measurements, have shown that the fastest reaction occurs with purine bases, by a mechanism involving both radical and singlet oxygen processes. The employed methodology can be of general use to investigate the mechanistic aspects of photosensitization by drugs. PHOTOSENSITIVITY SIDE EFFECTSThe combined action of drugs and sunlight on patients can produce both desired and undesired effects [1]. Thus, PUVA-therapy (psoralenes plus UVA-radiation) has long been employed for the treatment of psoriasis, while porphyrins are currently being introduced for the photodynamic therapy (PDT) of cancer or other diseases. By contrast, there is also a significant number of reports indicating that a variety of drugs can elicit undesired side effects, such as phototoxicity, photoallergy, or photocarcinogenicity [2,3].The photobiological risk associated with the use of drugs depends on environmental and individual factors (climate, height on the sea level, type of skin, etc.). On the other hand, the photosensitizing potential is enhanced in the case of topically administered drugs or when the field of application is dermatology or ophthalmology. Considering all these factors, in a number of cases it may be advisable to evaluate the photobiological risk of a new drug candidate before its introduction in the market [3]. The mechanistic approach to risk predictionIn order to anticipate the appearance of photosensitivity side effects, a mechanistic understanding of the involved phenomena is necessary. Absorption of sunlight by drugs leads to their excited states. These can proceed further to afford drug-derived reactive intermediates or, under aerobic conditions, reactive oxygen species. Any of the above short-lived chemical entities may be able to interact with biological *Lecture presented at the

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

“…For a better understanding of the photoinactivation process, the knowledge of how the molecular targets are affected by PDI assumes a great importance [ 113 ]. For this reason, a detailed photophysical and photochemical study of the interactions between the toxic species generated by the PS and key biomolecules such as lipids, proteins and nucleic acids is essential for the knowledge and prediction of photosensitization process efficiency [ 114 ]. However, the studies performed show that the primary target of PDI depends on the chemical structure of the PS, the targeted virus and the mechanism of photoinactivation [ 64 ].…”

Ambient UVA‐Induced Expression of p53 and Apoptosis in Human Skin Melanoma A375 Cell Line by Quinine

“…Skin phototoxicity is a common health problem, caused by the interaction of drugs with sunlight (24). The selection of different intensities of UVA irradiation proves our viewpoint that higher intensities of UVA during peak hours in sunlight would be more deleterious (17).…”

Photoinduced electron transfer photodegradation of photosensitive diuretic drug-xipamide

“…Such interest has been promoted by the fact that even though many of these compounds are excellent therapeutical agents, they are also known to often cause phototoxic and/or photoallergic phenomena [1][2][3]. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population.…”