Photosensitization by drugs: quinine as a photosensitizer.
Explore the source record for details and available documents.
Chemistry, Pharmaceutical↗
SEARCH · Search PubMed
Results for “PHOTOSENSITIZATION”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Mechanisms of photosensitized oxidation. There are several different types of photosensitized oxidation which may be important in biological systems.
Explore the source record for details and available documents.
Amines↗
[A comparative study on the photodynamic effect, photosensitive side action and toxicity of several China-made photosensitizers].
Explore the source record for details and available documents.
Animals↗
A comparison of type I and type II photosensitization and protection and the various roles of hydrogen bonding to substrates, photosensitizers, and intermediates.
Explore the source record for details and available documents.
Catalysis↗
Photosensitivity in epilepsy. Electrophysiological and clinical correlates.
Photosensitivity is a rare phenomenon found, often more or less accidentally, in approximately 5% of epileptic patients. Its pathophysiology still remains largely unsolved and the clinical significance of photosensitivity is controversial. The literature on the subject is impressive, yet predominantly anecdotal. In this thesis we describe the results of an extensive and standardized study of 100 consecutive photosensitive patients with special emphasis on the clinical history, the seizure history and the electrophysiological findings. These are then compared to identical data of an age and sex matched control group, obtained from the same population of epileptic patients, referred to a special (tertiary care) epilepsy clinic. In chapter I, the literature is reviewed and photosensitivity as a special form of "reflex epilepsy" is discussed. A distinction is made between normal and abnormal reactions on intermittent photic stimulation (IPS) during electroencephalographic (EEG) registrations and the criteria of true photosensitivity are formulated. The relation between the presence of photosensitivity during EEG examination and the occurrence of visually-induced epileptic seizures in daily life is discussed. As self-induction of seizures has been associated with photosensitivity, an extensive review, including a special reference list (see appendix A), is given concerning such self-inducing behaviour in photosensitive patients. A review of photosensitivity as a genetic marker and model of epilepsy concludes this chapter. In chapter II the aims of this study are outlined. Some general conceptions about photosensitive epilepsy have become widely accepted in clinical practice without much scientific support, i.e., the idea that the finding of photosensitivity is synonym with the diagnosis of primary generalized epilepsy. Furthermore, photosensitivity is generally believed to be a genetically determined, benign type of epilepsy in childhood and adolescence but when associated with self-inducing behaviour is interpreted as a sign of mental subnormality. Whether or not these conceptions are valid and whether photosensitivity is or is not a special subtype of epilepsy remains unsolved. In this study we thus set out to answer the following questions: A. Are photosensitive epileptic patients different from non-photosensitive patients with epilepsy, with respect to clinical history and, more specifically, to seizure history and family history for seizures? B. Is the degree of photosensitivity, established as photosensitivity range, predictive for the liability to visually-induced seizures in daily life? Are detailed laboratory findings concerning sensitivity to television and black-and-white striped patterns of clinically predictive value, e.g. can patients, liable to TV epilepsy or pattern-induced seizures, be identified by EEG investigations?
Adolescent↗
Phthalocyanine photodynamic therapy: disparate effects of pharmacologic inhibitors on cutaneous photosensitivity and on tumor regression.
The phthalocyanines are promising second-generation photosensitizers that are being evaluated for the photodynamic therapy (PDT) of malignant tumors. In vivo studies with the silicon phthalocyanine Pc 4 have shown that it is highly effective at causing regression of RIF-1 tumors in C3H/HeN mice in PDT protocols. Because cutaneous photosensitivity is the major complication of photosensitizers used for PDT, experiments were performed to evaluate the effect of inhibitors of the inflammatory response (cyproheptadine, dexamethasone, pentoxifylline, and tumor necrosis factor alpha [TNF-alpha] antibodies) on Pc 4-induced cutaneous photosensitivity and tumor regression. The C3H/HeN mice were injected with either Pc 4 or Photofrin and were exposed to 86 J/cm2 of filtered radiation emitted from a solar simulator. Animals were irradiated at 1, 3, 7, 10, 14 and 28 days postinjection. Cutaneous photosensitivity was assessed using the murine ear-swelling response. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies were administered prior to illumination to assess their ability to block Pc 4-induced cutaneous photosensitivity and to evaluate whether such treatment adversely influenced Pc 4 PDT-induced tumor regression. Compared to Photofrin, Pc 4 produced cutaneous photosensitivity that was transient, resolving within 24 h, and that could be elicited for only 10 days after administration. In contrast, Photofrin caused photosensitivity that required 4 days to resolve and could be elicited for at least 1 month after it was administered. The Pc 4-induced cutaneous photosensitivity could be blocked by corticosteroids and an inhibitor of vasoactive amines (cyproheptadine). The TNF-alpha gene transcription was found to increase in keratinocytes following treatment with Pc 4 and light. The anti-TNF-alpha antibodies and pentoxifylline, an inhibitor of cytokine transcription, also prevented cutaneous photosensitivity, implicating TNF-alpha in the pathogenesis of Pc 4-induced cutaneous photosensitivity. None of these agents had any effect on Pc 4 PDT-induced tumor regression. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies may be valuable pharmacologic agents in the management of cutaneous photosensitivity associated with PDT without altering the efficacy of this new therapeutic modality. The findings suggest that it should be possible to devise PDT protocols that block cutaneous photosensitivity without impairing the anti-tumor response to the agents.
Animals↗
[Incidence of drug-induced photosensitization during phototherapy].
BACKGROUND: Exogenous photosensitization represents one of the adverse effects of phototherapy. However, the impact of potentially photosensitizing drugs on the incidence of photo-induced eruptions during phototherapy is unknown. AIM OF THE STUDY: To determine the incidence of drug photosensitization during phototherapy. PATIENTS AND METHODS: This was a retrospective study of all patients undergoing phototherapy between November 1999 and April 2004 in the Dermatology Department of Caen University Teaching Hospital. Details of all topical or systemic medications taken before or during phototherapy were recorded. Since methoxsalen induces photosensitization, sessions of phototherapy were stratified according to whether methoxsalen was given. Screening was performed for the following clinical signs of drug photosensitization: acute photo-induced, erythematous and/or vesicular eruption, associated with pruritus or burning. RESULTS: In the non-methoxsalen group, use of a potentially photosensitizing drug was found for 29/155 TL01 phototherapy sessions. Drug-induced photosensitization was suspected in 3/29 sessions (10.3%). In the methoxsalen group, a potentially photosensitizing drug was found in 21/118 sessions of PUVA-therapy. Drug-induced photosensitization was suspected in 4/21 sessions (19%). Risk of photo-induced eruption was not associated with photosensitizing drug therapy, TL01 phototherapy or PUVA-therapy. DISCUSSION: Drug photosensitization appears to be rare during phototherapy, regardless of photosensitizing drug intake. It is twice as frequent during PUVA-therapy as during TL01 phototherapy but this difference is not significant.
Adolescent↗
Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy.
Photodynamic therapy (PDT) is a promising new treatment modality for several diseases, most notably cancer. In PDT, light, O2, and a photosensitizing drug are combined to produce a selective therapeutic effect. Lately, there has been active research on new photosensitizer candidates, because the most commonly used porphyrin photosensitizers are far from ideal with respect to PDT. Finding a suitable photosensitizer is crucial in improving the efficacy of PDT. Recent synthetic activity has created such a great number of potential photosensitizers for PDT that it is difficult to decide which ones are suitable for which pathological conditions, such as various cancer species. To facilitate the choice of photosensitizer, this review presents a thorough survey of the photophysical and chemical properties of the developed tetrapyrrolic photosensitizers. Special attention is paid to the singlet-oxygen yield (PhiDelta) of each photosensitizer, because it is one of the most important photodynamic parameters in PDT. Also, in the survey, emphasis is placed on those photosensitizers that can easily be prepared by partial syntheses starting from the abundant natural precursors, protoheme and the chlorophylls. Such emphasis is justified by economical and environmental reasons. Several of the most promising photosensitizer candidates are chlorins or bacteriochlorins. Consequently, chlorophyll-related chlorins, whose PhiDelta have been determined, are discussed in detail as potential photosensitizers for PDT. Finally, PDT is briefly discussed as a treatment modality, including its clinical aspects, light sources, targeting of the photosensitizer, and opportunities.
Photochemotherapy↗
Differential response of photosensitized young and old human erythrocytes to photodynamic activation.
It has recently been proposed that photosensitized erythrocytes may play an important role in the delivery and targeting of agents such as photosensitizers and chemotherapeutics for use in cancer treatment. It has been suggested that loading of photosensitized erythrocytes with chemotherapeutic agents would provide an ideal means of combining both treatment modalities. The recent application of real-time confocal laser scanning microscopy to the study of immediate effects of photodynamic activation on photosensitized erythrocytes has enabled us, in this study, to distinguish between the differential susceptibility of age-density resolved sub-populations of human erythrocytes to photodynamic activation. In this study we demonstrate that younger (low age-density) sub-populations of photosensitized erythrocytes are less susceptible than older (high age-density) sub-populations to photodynamic activation. We also demonstrate that this phenomenon is exhibited by cells photosensitized using hematoporphyrin derivative and rose bengal as photosensitizers. In both cases no significant difference in uptake of photosensitizer by both populations could be observed using absorbance spectrophotometry. The study suggests that age-density resolution of erythrocytes prior to loading and photosensitization might provide a means of enhancing the release of loaded components from the photosensitized system and this would, in turn, enhance the potential use of photosensitized erythrocytes as delivery or targeting systems for use in combination cancer therapies.
Cell Separation↗
Experimental study on phototoxicity and the photosensitization potential of ketoprofen, suprofen, tiaprofenic acid and benzophenone and the photocross-reactivity in guinea pigs.
BACKGROUND: Ketoprofen, suprofen and tiaprofenic acid are arylpropionic anti-inflammatories. Their chemical structures share the same elements as the benzoyl radical and the tiophene ring. We experienced nine cases of ketoprofen photoallergy, seven cases of suprofen photoallergy and three cases of tiaprofenic photoallergy. PURPOSE: To find the key structure of photosensitivity and photocross-reactivity to ketoprofen, suprofen and tiaprofenic acid. METHODS: : Three animals were tested for phototoxicity and six animals for the photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone, and the photocross-reactivity of the above chemicals. Test substances were applied symmetrically on both sides of the animals' backs. The animals were irradiated with 180 mJ/cm2 UVB ((1/2) MED) and 10 J/cm2 UVA on the left side. The reactions were read on days 2, 3 and 4. The photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone were determined using the Adjuvant-Strip method. Six animals were assigned to each test group and to a control group. RESULTS: Ketoprofen, suprofen, tiaprofenic acid and propionic acid showed negative reactions with the phototoxic test. Benzophenone showed phototoxic reactions to 40% acetone (ac.), 20% ac. and 10% ac. Therefore, we used 5% aq. benzophenone with the photosensitization test. Ketoprofen was the strongest photosensitizer (6/6) and showed photocross-reactivities to suprofen (2/6), tiaprofenic acid (3/6) and benzophenone (6/6). Suprofen was a strong photosensitizer (4/6) and showed photocross-reactivities to ketoprofen (1/4) and tiaprofenic acid (2/4), but not to benzophenone. Tiaprofenic acid was also a photosensitizer (2/6) but showed a photocross-reactivity only to benzophenone (2/2). Benzophenone was also the strongest photosensitizer (6/6), but did not photocross-react to the above three chemicals. CONCLUSION: From the test results, it appears that benzoyl radical is the key structure for photosensitivity and the photocross-reactivity of ketoprofen, suprofen and tiaprofenic acid. The whole structure of benzophenone was needed to induce photosensitization of benzophenone. The animals that were photosensitized from the entire structure of benzophenone did not photocross-react to ketoprofen, suprofen or tiaprofenic acid.
Animals↗
Protective action of beta-carotene against lethal photosensitization of fibroblasts in vitro.
Cell culture experiments using haematoporphyrin photosensitized bovine hoof fibroblasts and long-wave uv-irradiation revealed two distinct and separable patterns of lethal photosensitization according to two different sensitization procedures: (1) Photosensitization of cell membranes by short exposure (5 min) of cells to haematoporphyrin. (2) Cytoplasmic photosensitization elicited by a 2 h exposure of cells to haematoporphyrin. Cell membrane photosensitization was reversible by incubation of cells in serum which removed surface bound haematoporphyrin; cytoplasmic photosensitization was irreversible. Beta-carotene was tested in these two systems and the following results were obtained: (1) Preincubation of bovine hoof fibroblasts in beta-carotene protects from lethal haematoporphyrin photosensitization. (2) Protection with beta-carotene is achieved against both types of photosensitization. (3) The protective effect of beta-carotene depends upon the duration of pretreatment, reaching a maximum after 7 days. (4) Beta-carotene protection is maintained even after trypsinization of bovine hoof fibroblasts and withdrawal of beta-carotene from the medium for 24 h or more. (5) Haematoporphyrin sensitized bovine hoof fibroblasts show a distinct pattern of red fluorescence for each type of photosensitization. Incubation of bovine hoof fibroblasts in beta-carotene prior to haematoporphyrin photosensitization results in a pronounced reduction of red fluorescence. Some of these data indicate that beta-carotene acts, at least in cell membrane photosensitization, at the level of the cell membrane into which it appears to be incorporated.
Animals↗
Photosensitivity in lupus erythematosus.
BACKGROUND: Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. METHODS: Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. RESULTS: Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide synthase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor alpha also seems to play a role in the development of photosensitivity. CONCLUSION: The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor alpha polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sine qua non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity.
Apoptosis↗
Inheritance of photosensitivity.
PURPOSE: To investigate the mode of inheritance of the photoparoxysmal response (PPR) and to obtain more information about the influence of photosensitivity on the seizure risk in siblings of patients with epilepsy. METHODS: Examination of the records of families with one photosensitive parent (Group I, n = 54) and of families with a photosensitive proband, neither of whose parents was photosensitive (Group II, n = 72). RESULTS: At the age of maximum penetrance, between 5 and 15 years of age, 50% of the siblings in Group I were photosensitive, compared to only 15% in Group II. Siblings in Group I showed a higher seizure rate (19%) than siblings in Group II (4%, p < 0.005). The majority of photosensitive siblings had no seizures, but photosensitive siblings had a higher seizure risk than non-photosensitive siblings. The highest seizure risk was found in photosensitive siblings of Group I (33%) compared to 9% in non-photosensitive siblings (p < 0.05). CONCLUSION: Our findings show that a PPR in parents is a major determinant for the risk of a PPR in offspring. The results may indicate an autosomal-dominant transmission with age-dependent penetrance of the PPR. Photosensitivity is an important factor in the pathogenesis of seizure disorders in childhood.
Adolescent↗
A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.
Prior studies, both in vitro and in vivo, have suggested that cutaneous porphyrin photosensitization requires the generation of superoxide anion (.O2-) and various other reactive oxygen metabolites. No unifying concept has emerged, however, that unequivocally demonstrates the source of generation of these species. Since xanthine oxidase is known to generate .O2- in reperfused ischemic tissue and in certain inflammatory disorders, we attempted to assess its role in porphyrin photosensitization. C3H mice were rendered photosensitive by the intraperitoneal administration of dihematoporphyrin ether (DHE) (5 mg/kg) followed by irradiation with visible light. Murine ear swelling was used as a marker of the acute photosensitization response and involvement of oxygen radicals was evaluated using electron spin resonance (ESR) spectroscopy. The administration of allopurinol, a potent inhibitor of xanthine oxidase, afforded 90% protection against DHE-mediated acute photosensitivity in vivo. Furthermore, xanthine oxidase activity was twofold higher in the skin of photosensitized mice than in unirradiated animals. ESR spectra of 5,5-dimethyl-1-pyrroline N-oxide-trapped radicals from the skin of photosensitized mice verified the presence of .O2- and .OH, while neither of these species was detected in the skin of control mice or mice receiving allopurinol. The administration of a soybean trypsin inhibitor or verapamil before irradiation also partially blocked the photosensitivity response, suggesting that calcium-dependent proteases play a role in the activation of xanthine oxidase in this photodynamic process. These data provide in vivo evidence for the involvement of .O2- in DHE-mediated cutaneous photosensitization and suggest that these radicals are generated through the activation of the xanthine oxidase pathway. The administration of allopurinol and calcium channel blockers may thus offer new approaches for the treatment of cutaneous porphyrin photosensitization.
Allopurinol↗
Photosensitivity in lupus.
A wide variety of skin conditions may present in patients with lupus erythematosus (LE). These can be broadly divided into three main groups: cutaneous forms of LE ('LE-specific skin disease'), non-specific cutaneous manifestations of SLE ('LE non-specific skin disease') and cutaneous complications of drug treatments for LE. This review examines clinical photosensitivity in LE, a trait most commonly associated with cutaneous forms of LE but which may also manifest in SLE. All humans are photosensitive, developing reddening of the skin if exposed to sufficient ultraviolet radiation (UVR). Therefore we define photosensitivity in clinical practice as an abnormal cutaneous response to UVR. Abnormal photosensitivity in LE may manifest in a number of different forms. The lesions of LE-specific skin disease may be induced or exacerbated by UVR. Patients with LE who are prescribed photosensitizing medications such as thiazide diuretics, neuroleptics and tetracyclines may also develop phototoxic reactions which usually present as easy sunburn. Photosensitivity may also, rarely, manifest as fragile skin and blistering in patients with both LE and porphyria cutanea tarda. Several other photosensitive disorders have been reported in association with LE, including solar urticaria and erythropoetic protoporphyria (EPP), but these appear to be chance associations. Assessment of patients with LE and photosensitivity requires a careful history and examination. Phototesting and photoprovocation tests may be used to demonstrate photosensitivity in some cases, but these are rarely required for diagnosis. Photosensitive patients should be advised about sun avoidance, photoprotection and sunscreen use as a first line treatment.
Humans↗
Augmentation of 12-O-tetradecanoyl 13-phorbol acetate-mediated tumor promoting response by the porphyrin photosensitization of 7,12-dimethyl benz[a]anthracene-initiated murine skin: role of in situ generated reactive oxygen species.
Recently, we have shown that sustained ROS generation by prolonged porphyrin-mediated photosensitization in murine skin acts as a stage I and weak complete tumor promoter. Further to this, in the present study, we show that porphyrin photosensitization of DMBA-initiated murine skin results in the augmentation of TPA-mediated tumor promoting response. The photosensitization increased tumor yield to 15 tumors per mouse as compared to 7.5 tumors per mouse in the group treated with TPA alone. Further, 100% tumor incidence in the TPA-treated photosensitized group occurred at week 11 whereas it occurred at week 19 in the TPA alone treated group. Porphyrin photosensitization slightly decreased the latency period of TPA-mediated tumor formation by 1 week. The TPA-mediated ODC induction (1300% of saline-treated control) has been augmented in the photosensitized group (1950%). However, the amount of [3H]thymidine incorporation was not significantly different in the photosensitized TPA-treated and TPA alone-treated groups. Similarly, TPA treatment in photosensitized animals augmented the depletion of cutaneous glutathione and enhancement of lipid peroxidation. These changes were attenuated in butylated hydroxytoluene-pretreated animals. Our results suggest that cutaneous porphyrin photosensitization augments TPA-mediated tumor promotion in murine skin.
9,10-Dimethyl-1,2-benzanthracene↗
Comparative study of lethal photosensitization of Sarcina lutea by 8-methoxypsoralen and by toluidine blue.
Mathews, Micheline M. (Department of Bacteriology, University of California, Berkeley). Comparative study of lethal photosensitization of Sarcina lutea by 8-methoxypsoralen and by toluidine blue. J. Bacteriol. 85:322-328. 1963.-A comparative study has been made of the photo-killing of Sarcina lutea by 8-methoxypsoralen (8-MOP) and by toluidine blue. It has been found that photosensitization by 8-MOP differs from photosensitization by toluidine blue, in that it has a temperature coefficient of less than one, and that the presence of oxygen is not necessary for, and even is deleterious to, the photosensitization, the psoralen being destroyed by its presence. It has previously been shown that the presence of carotenoid pigments protects the cells of S. lutea from lethal photosensitization by toluidine blue; it was found that the presence of these pigments has no protective effect in photosensitization with 8-MOP. Studies on the lethal photosensitization of S. lutea with toluidine blue suggested that the primary sensitive site of the photokilling was the protein of the cell membrane, as manifested by the destruction of membrane enzyme activity and the regulation of permeability. It has been found that photokilling by 8-MOP has no effect on these functions. A study was made on the effect of photokilling by 8-MOP on the production of penicillin-resistant mutants as an indication of an alteration in the cellular deoxyribonucleic acid (DNA) by the psoralen. Psoralen photosensitization resulted in the development of many penicillin-resistant mutants. On the basis of the findings reported in this paper, it is suggested that photosensitization of S. lutea by 8-MOP does not reflect damage to cellular protein, as does toluidine blue, but rather damage to cellular DNA.
Cell Membrane↗
Parenchymal injury and biliary obstruction in relation to photosensitization in sporidesmin-intoxicated lambs.
The hepatic changes were compared in lambs photosensitized or not photosensitized after exposure to sporidesmin. Injury to both the parenchyma and the biliary system was more severe in the photosensitized than in the non-photosensitized lambs. The activities of gamma-glutamyltransferase and glutamate dehydrogenase, and the total, conjugated and unconjugated bilirubin concentrations were significantly higher in sera from the photosensitized than from the non-photosensitized lambs. Hepatic glycogen levels were decreased in both the photosensitized and the non-photosensitized lambs, but were significantly lower in the former. Hence it is possible that lesions in hepatocytes contribute to retention of phylloerythrin and so to photosensitization.
Animals↗