A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species

Baek, Seung Jae; Chang, Jae Won; Park, Keun Hyung; Yang, Garp Yeol; Hwang, Hye Sook; Koh, Yoon Woo; Jung, Young Sik; Kim, Chul Ho

doi:10.3349/ymj.2014.55.4.886

Cited by 3 publications

(1 citation statement)

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“…These proteins in turn activate downstream caspases signaling to execute the IR-induced apoptotic signal. A study by Baek et al ( 41 ) has demonstrated that KR22332 has minimized radiation-induced (8 Gy) apoptosis by retaining the mitochondrial transmembrane potential in HaCat cells. In line with this report, G-003M pretreatment also regulated IR-induced alteration in mitochondrial membrane integrity by maintaining optimum level of MMP in both the bone marrow cells and splenocytes.…”

Section: Discussionmentioning

confidence: 99%

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

et al. 2017

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The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (−1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury.

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Section: Discussionmentioning

confidence: 99%

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

et al. 2017

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Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinolinone derivatives as potential chitin synthase inhibitors and antifungal agents

Shen

et al. 2020

European Journal of Medicinal Chemistry

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Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies

Nguyen

Sangha

Pan

et al. 2022

IJMS

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Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.

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A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species

Cited by 3 publications

References 20 publications

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinolinone derivatives as potential chitin synthase inhibitors and antifungal agents

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies

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