High-throughput reactive oxygen species (ROS) assay: An enabling technology for screening the phototoxic potential of pharmaceutical substances

Onoue, Satomi; Igarashi, Naoko; Yamada, Shizuo; Tsuda, Yoshiko

doi:10.1016/j.jpba.2007.09.003

Cited by 54 publications

(56 citation statements)

References 16 publications

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“…Then cells were collected and suspended within 500 µL PBS, and fluorescent intensities were measured by using a flow cytometer at 488 nm excitation and 521 nm emission [23].…”

Section: Reactive Oxygen Species (Ros) Assaymentioning

confidence: 99%

Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

et al. 2013

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“…Then cells were collected and suspended within 500 µL PBS, and fluorescent intensities were measured by using a flow cytometer at 488 nm excitation and 521 nm emission [23].…”

Section: Reactive Oxygen Species (Ros) Assaymentioning

confidence: 99%

Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

et al. 2013

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“…2B) since the good relationship between ROS data on chemicals at 200 mM and in vivo phototoxicity revealed the prediction capacity of the ROS assay (Onoue and Tsuda, 2006;Onoue et al, 2008a). FF and FA exhibited potent generation of singlet oxygen, with values of 463 and 531 (DA 440 nm Â 10 3 ), respectively; they also generated superoxide, with values of 171 and 332 (DA 560 nm Â 10 3 ).…”

Section: Resultsmentioning

confidence: 98%

“…Generation of superoxide and singlet oxygen from photoirradiated chemicals can be reliable indicators of type I and II photochemical reactivity, respectively (Onoue and Tsuda, 2006;Onoue et al, 2008a).…”

Section: Discussionmentioning

confidence: 99%

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

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Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M 21 cm 21 (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins.

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“…This study tested three compounds that were known to have phototoxicity (8-MOP, acridine, and anthracene) and 19 drugs that have been shown to have phototoxic potential (amlodipine, benzoyl peroxide, bufexamac, chlorpromazine, diclofenac, furosemide, haloperidol, ibuprofen, indomethacin, ketoprofen, naproxen, nifedipine, nimodipine, nitrendipine, promethazine, piroxicam, quinine, retinol, and tamoxifen) (Onoue and Tsuda, 2006;Onoue et al, 2008). The compounds 8-MOP, acridin, and anthracene were dissolved in acetone to give 0.2, 1, and 0.3 w/v% solutions, respectively, following a previous report (Lovell and Sanders, 1992).…”

Section: Transdermal Administration Studymentioning

confidence: 99%

“…SD rats are widely used to measure PK profile, which is usually measured before phototoxicity, and therefore it would be more efficient to use them in phototoxicity studies too. For this work, the chosen test compounds were drugs that had already been found to have phototoxic potential based on reactive oxygen species (ROS) assays (Onoue and Tsuda, 2006;Onoue et al, 2008;Seto et al, 2011Seto et al, , 2013. ICH guidelines indicate that the ROS assay is a reliable indicator of phototoxicity (ICH, 2013).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration

et al. 2015

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-Guinea pigs are the most frequently used animals in phototoxicity studies. However, general toxicity studies most often use Sprague-Dawley (SD) rats. To reduce the number of animals needed for drug development, we examined whether skin phototoxicity studies could be performed using SD rats. A total of 19 drugs that had previously been shown to have phototoxic potential and 3 known phototoxic compounds were administered transdermally to guinea pigs and SD rats. Eleven of the potentially phototoxic drugs and 2 of the known phototoxic compounds were also administered orally to guinea pigs and SD rats. After administration, the animals were irradiated with UV-A (10 J/cm 2 ) and UV-B (0.25 J/cm 2 in guinea pigs and 0.031 J/cm 2 in SD rats) with doses based on standard phototoxicity study guidelines and the results of a minimum erythema dose test, respectively. In the transdermal administration study, all of the known phototoxic compounds and 7 of the drugs induced phototoxic reactions. In the oral administration study, both known phototoxic compounds and 5 drugs induced phototoxic reactions in both species; one compound each was found to be toxic only in SD rats or guinea pigs. The concordance rate of guinea pigs and SD rats was 100% in the transdermal administration study and 85% in the oral administration study. This study demonstrated that phototoxicity studies using SD rats have the same potential to detect phototoxic compounds as studies using guinea pigs.

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High-throughput reactive oxygen species (ROS) assay: An enabling technology for screening the phototoxic potential of pharmaceutical substances

Cited by 54 publications

References 16 publications

Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

Inducible miR-145 expression by HIF-1α protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration

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