Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting in mitochondrial depolarization and lysosomal destabilization

Ray, Ratan Singh; Mujtaba, Syed Faiz; Dwivedi, Ashish; Yadav, Neera; Verma, Ankit; Kushwaha, Hari Narayan; Amar, Saroj Kumar; Goel, Sudhir K.; Chopra, Deepti

doi:10.1016/j.tox.2013.10.002

Cited by 31 publications

(21 citation statements)

References 26 publications

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“…After incubation, medium was replaced with new MTT (5 mg/mL) containing medium and incubate for 3 hours. After incubation, cells containing MTT were replaced with dimethyl sulfoxide and optical density (OD) has been recorded at 540 nm through enzyme‐linked immunosorbent assay (ELISA) reader …”

Section: Methodsmentioning

confidence: 99%

Biochemical regulation and structural analysis of copper‐transporting ATPase in a human hepatoma cell line for Wilson disease

Agnihotry

Dhusia

Srivastav

et al. 2019

J of Cellular Biochemistry

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Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depending on the dietary intake, copper bioavailability, and genetic factors. Copper chloride (CuCl2) caused dose‐dependent reduction in cell viability of human teratocarcinoma (HepG2) cell line, measured using the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Cells were exposed to different concentrations of CuCl2 in log doses and maximum cell viability reduction was recorded at 15 µg/mL. Toxic dose of CuCl2 is potent inducer of reactive oxygen species (ROS). Apoptosis as a pattern of cell death was confirmed through sub‐G1 fraction and morphological changes such as mitochondrial depolarization, endoplasmic reticulum and lysosomal destabilization, phosphatidylserine translocation, and DNA damage. Our transcriptional and translational results strongly support apoptotic cell death. Using the available data present in dbSNP and bioinformatics tools, three nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified as deleterious, reducing the stability of protein ATP7B. Structural analysis of native and mutant ATP7B proteins was investigated using molecular dynamics simulation (MDS) approach. Mutation in ATP7B gene might disturb the structural conformation and catalytic function of the ATP7B protein may be inducing WD. Hence, excess dietary intake of copper chloride must be avoided for safety of health to prevent from WD.

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Section: Methodsmentioning

confidence: 99%

Biochemical regulation and structural analysis of copper‐transporting ATPase in a human hepatoma cell line for Wilson disease

Agnihotry

Dhusia

Srivastav

et al. 2019

J of Cellular Biochemistry

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“…44 Aniline without halogenated substituent has the higher k Q value than the compounds with chlorine and bromine in acetonitrile, possibly due to halogens (-F, -Cl and -Br) are electron withdrawing groups (EWGs) and inefficient for electron delocalization, hence with a lower capacity to stabilize resonance structures. [4][5] For instance, the quenching rates are 9.0 x 10 3 M -1 s -1 for stearic acid, 1.7 x 10 4 M -1 s -1 for oleic acid, 4.2 x 10 4 M -1 s -1 for linoleic acid, 5.7 x 10 4 M -1 s -1 for cholesterol, and 5.1 x 10 5 M -1 s -1 for DNA. [45][46][47] The interest in obtaining this type of heterocyclic chalcone derivatives is due to their versatility as starting materials in the synthesis of a series of heterocyclic compounds.…”

Section: Overall Rate Constants (K Q ) For the Quenching Of 1 Omentioning

confidence: 99%

“…Its unique reactivity in a number of photochemical processes in a variety of systems 1-3 including e. g. lipids, sterols, proteins, DNA, and RNA [4][5] results in the degradation of biological systems and cell death. Its unique reactivity in a number of photochemical processes in a variety of systems 1-3 including e. g. lipids, sterols, proteins, DNA, and RNA [4][5] results in the degradation of biological systems and cell death.…”

Section: Introductionmentioning

confidence: 99%

Novel (E)-1-(pyrrole-2-yl)-3-(aryl)-2-(propen-1-one) derivatives as efficient singlet oxygen quenchers: kinetics and quantum chemical calculations

et al. 2015

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†Electronic Supplementary InformaƟon (ESI) available: Cartesian coordinates (and geometries) of the ground and first triplet states computed by quantum chemical calculations as well as the IR and NMR experimental spectra are presented. See Chalcones constitute an important group of natural and synthetic products that have been screened due to their wide range of pharmacological applications. Herein, we studied the antioxidant activity of five newly synthetized (E)-1-(pyrrole-2-yl)-3-(aryl)-2-(propen-1-one) (PAPs) derivatives against singlet oxygen ( 1 O2). The differences among the compounds are related to the aryl substitution in the p-position where: 3a = C6H5, 3b = 4-H3COC6H4, 3c = 4-FC6H4, 3d = 4-ClC6H4, 3e = 4-BrC6H4. The PAPs were synthesized by Claisen-Schmidt condensation reaction between 2-acetylpyrrole and aromatic aldehydes under ultrasonic irradiation (yields between 79-86%) and were characterized by IR, mass spectrometry, NMR and quantum chemical calculations. The total singlet oxygen quenching rate constants (kQ) by the PAPs were measured spectrophotometrically in ethanol at 25 °C and determined by using the Stern-Volmer model. As the character of the EWGs is increased from 3a to 3e, the kQ diminishes smoothly. The best quencher is found to be the 3a compound (where the aryl group is unsubstituted) with a kQ = 5.71 (±0.21) x10 7 M -1 s -1 , which is similar to those for other antioxidants e.g. flavonoids. These results suggest these compounds as efficient quenchers of singlet oxygen and their potential aplicability in biological systems.

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“…Topical dosing avoids the gastrointestinal adverse events associated with oral dosing. Although more commonly associated with photoallergic reactions, photodegradation of ketoprofen occurs even under ambient UV intensities, resulting in the generation of singlet oxygen, and the subsequent promotion of mutagenic thymine dimers and strand breaks in DNA . The absorption maxima of ketoprofen, like many propionic acid‐derived NSAIDS, lies in the UVA range, suggesting the drug's capacity for a phototoxic reaction .…”

Section: Clinical Featuresmentioning

confidence: 99%

Drug-induced photosensitivity: new insights into pathomechanisms and clinical variation through basic and applied science

et al. 2017

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Drug-induced photosensitivity occurs when a drug is capable of absorbing radiation from the sun (usually ultraviolet A) leading to chemical reactions that cause cellular damage (phototoxicity) or, more rarely, form photoallergens (photoallergy). The manifestation varies considerably in presentation and severity from mild pain to severe blistering. Despite screening strategies and guidelines in place to predict photoreactive drugs during development there are still new drugs coming onto the market that cause photosensitivity. Thus, there is a continuing need for dermatologists to be aware of the different forms of presentation and the culprit drugs. Management usually involves photoprotection and cessation of drug treatment. However, there are always cases where the culprit drug is indispensable. The reason why some patients are susceptible while others remain asymptomatic is not known. A potential mechanism for the phototoxic reactions is the generation of reactive oxygen species (ROS), and there are a number of reasons why some patients might be less able to cope with enhanced levels of ROS.

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Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting in mitochondrial depolarization and lysosomal destabilization

Cited by 31 publications

References 26 publications

Biochemical regulation and structural analysis of copper‐transporting ATPase in a human hepatoma cell line for Wilson disease

Biochemical regulation and structural analysis of copper‐transporting ATPase in a human hepatoma cell line for Wilson disease

Novel (E)-1-(pyrrole-2-yl)-3-(aryl)-2-(propen-1-one) derivatives as efficient singlet oxygen quenchers: kinetics and quantum chemical calculations

Drug-induced photosensitivity: new insights into pathomechanisms and clinical variation through basic and applied science

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