Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions

Blotz, Andrea; Michel, Laurence; Moysan, A.; Blümel, Jörg; Dubertret, Louis; Ahr, H J; Vohr, Hans-Werner

doi:10.1016/s1011-1344(00)00097-x

Cited by 17 publications

(5 citation statements)

References 34 publications

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“…Irritation and inflammation. Photosensitization testing models, such as the Integrated Model for the Differentiation of chemical‐induced allergic and irritant Skin reactions (IMDS) (96), ensure an affordable screening of FQ phototoxicity. These tests allow determining how a compound may react after application to the skin and irradiated with solar simulated light.…”

mentioning

confidence: 99%

“…These cannot be easily detected by other existing assays. Indeed, the in vitro tests are of proven value only in predicting irritant or toxic effects (96). ENO, SPA, BAY, LOM, OFL were tested by IMDS on guinea pig (96).…”

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confidence: 99%

“…Indeed, the in vitro tests are of proven value only in predicting irritant or toxic effects (96). ENO, SPA, BAY, LOM, OFL were tested by IMDS on guinea pig (96). Skin photoirritation was evaluated and scored by the appearance of erythema and swelling of the mice ears at various times after irradiation (91).…”

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confidence: 99%

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Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Guidi

Bracchitta

Catalfo

2011

Photochem & Photobiology

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This review focuses on damage photosensitized by the fluoroquinolone (FQ) antibacterial drugs. Different models are employed to study biosubstrate photodamage mediated by FQs (organisms, cells, isolated biomolecules and super molecules). Being that the effect of environment (polarity of the medium, ions, pH, binding with bio-molecules, etc.) is crucial in FQ photochemistry, photobiological reactions can be consequently dramatically influenced. Thus, the photosensitization processes induced by FQs are here discussed taking into account that such extensive and cross-targeted pathological implications request an excursus covering photosensitization in systems of increasing molecular complexity. In vivo and in vitro evidences for photoallergy, phototoxicity, photomutagenesis and photocarcinogenesis mediated by FQs are discussed.

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Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Guidi

Bracchitta

Catalfo

2011

Photochem & Photobiology

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“…Various in vivo models have used mice, rats and guinea pigs for phototoxicity testing. [4][5][6][7] In vitro assays, such as the 3T3 Neutral Red Uptake phototoxicity assay (3T3 NRU PT assay; OECD TG 432) and the phototoxicity test with reconstructed human epidermis (RhE Phototoxicity Test (RhE PT); OECD TG 498), have been introduced as alternative methods for phototoxicity testing. Since the publication of the ICH S10 guideline on the photosafety assessment of pharmaceuticals, 8 by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the interest in photosafety assessment has further increased as part of the pharmaceutical development process.…”

Section: Introductionmentioning

confidence: 99%

In Silico Phototoxicity Prediction of Drugs and Chemicals by using Derek Nexus and QSAR Toolbox

Ahuja,

Adiga Perdur,

et al. 2024

Altern Lab Anim

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Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional in vivo models involving mice, rats, guinea pigs, as well as in vitro assays such as the 3T3 Neutral Red Uptake phototoxicity assay and methods based on the use of reconstructed human epidermis, have been established for phototoxicity testing. While these approaches are extremely valuable, they are costly in terms of both time and resources. Consequently, in silico approaches based on the use of predictive software tools can offer more rapid and cost-effective phototoxicity screening solutions. With this goal in mind, the current study evaluated two in silico tools — Derek Nexus 6.1.0/Derek Knowledge Base 2020 1.0 (Lhasa Limited, UK) and the QSAR Toolbox (v 4.5) developed by the Organisation for Economic Co-operation and Development (OECD) — for their capacity to predict the phototoxicity of several substances from diverse classes. Derek Nexus and the QSAR Toolbox were both found to be very useful for predicting the phototoxicity of drugs and other chemicals. Derek Nexus predicted phototoxicity of the compounds, with a sensitivity of 63%, specificity of 93%, Positive Predictive Values of 90% and Negative Predictive Value of 69%, overall accuracy of 77% and balanced accuracy of 78%. The QSAR Toolbox achieved sensitivity of 73%, specificity of 85%, Positive Predictive Value of 85% and Negative Predictive Value of 74%, overall accuracy of 79% and balanced accuracy of 79%. The results show that Derek Nexus and the QSAR Toolbox can be usefully incorporated in the workflow of phototoxicity testing for pharmaceuticals and chemicals.

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“…Recently, the alternative methods to the sensitization such as local lymph node assay (LLNA) and an integrated model for the differentiation of chemical-induced allergic and irritant skin reaction (IMDS) have been studied and developed by many researchers. And validation studies on the alternative methods to the sensitization are in progress (Blotz et al , 2000 ; Loveless et al , 1996 ; Ulrich et al , 1998 ; Vohr et al , 1994 , 2000) . The IMDS (Homey et al , 1998) is a new method amending the defects of LLNA that uses the isotopes.…”

Section: Introductionmentioning

confidence: 99%

Safety Evaluation and Anti-wrinkle Effects of Retinoids on Skin

Kim¹

2010

Toxicological Research

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Retinoids have many beneficial effects on dermatological applications. But, retinoids cause skin irritation. In this study, the safety of retinoids was clarified via both primary skin irritation test in rabbits and sensitization study using an integrated model for the differentiation of chemical-induced allergic and irritant skin reaction (IMDS) , an alternative method to sensitization test. The effects of retinoids on the change of ultraviolet A (UVA) -induced matrix metalloproteinase-1 (MMP-1) in human skin fibroblasts and the modulation of type-1 pN collagen synthesis in hairless mice were examined to clarify the anti-wrinkle effects. All-trans retinol (t-ROL) and its derivative, all-trans retinoic acid (t-RA) , showed mild skin irritation but did not induce the sensitization. t-ROL and t-RA exerted anti-wrinkle effects by inhibiting the UVA-induced MMP-1 in human skin fibroblasts and increasing the type-1 pN collagen synthesis in hairless mice. These findings suggest that retinoids do not induce the allergy, and show anti-wrinkle effects by decreasing MMP-1 activation and increasing collagen synthesis.

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Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions

Cited by 17 publications

References 34 publications

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

In Silico Phototoxicity Prediction of Drugs and Chemicals by using Derek Nexus and QSAR Toolbox

Safety Evaluation and Anti-wrinkle Effects of Retinoids on Skin

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