Protective effect of epigallocatechin-3-gallate on ischemia/reperfusion-induced injuries in the heart: STAT1 silencing flavonoid

Darra, Elena; Shoji, Kazuo; Mariotto, Sofia; Suzuki, Hisanori

doi:10.1007/s12263-007-0060-3

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…12-14 EGCG has also been shown to suppress interferon gamma-induced phosphorylation of STAT1 at its Ser 727 and Tyr 701 residues in cancer cells and to suppress cisplatin-induced phosphorylation selectively Ser 727 in response to cisplatin in the cochlea. 4 In aspiration-induced lung tissue injury, pre-treatment with EGCG reduced levels of cytokines (TNFα and IL-1), of activated STAT1 protein, and of phosphorylated protein levels of JAK1 and JAK2, 15 which may be attributed to blockade of INF-γ induced STAT1 activation.…”

Section: Discussionmentioning

confidence: 99%

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Jiang

Ray

Rybak³

et al. 2016

Otology &Amp; Neurotology

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Rationale Oxidative stress plays a critical role in gentamicin-induced hair cell death. Prior work has implicated the cytoplasmic transcription factor STAT1 as a potential mediator of drug-induced ototoxicity, but role in aminoglycosides is largely unknown. This study investigated aminoglycosides-induced cell death, exploring contributions of reactive oxygen species and STAT1 pathway in injury and protection. Methods Neonatal murine organ of Corti explants from 2-3 day postnatal pups (n=96) were treated with gentamicin at (4 μΜ, 50 μΜ) for 4-72 hours, with/without protectants. Effects on STAT1 pathway and gentamicin-induced hair cell death were measured with 50 μΜ Epigallocatechin Gallate (EGCG, a STAT1 inhibitor) and all-trans retinoic acid (atRA, a STAT1 activator). Hair cell morphology was evaluated and hair cell loss was quantified with cytocochleograms. Mitochondrial membrane potential was assayed and superoxide generation and suppression was measured with dihydroethidium (DHE) staining. Results Co-administration of 50 μΜ EGCG conferred protection from 4 μΜ gentamicin toxicity (p < 0.001), whereas atRA potentiated gentamicin-induced hair cell death (p<.001). On immunohistochemistry, STAT1 phosphorylation at theserine 727 (Ser727) residues was increased at 72 hours with 4 μΜ gentamicin. With administration of 50 μΜ gentamicin, there was activation of STAT1 Tyr701 at 4 hours and STAT1 Ser727 at 16 hours. Gentamicin dissipated mitochondrial membrane potentials, and EGCG attenuated gentamicin-induced oxidative stress at 72 hours. Conclusion EGCG protected outer hair cells from gentamicin toxicity in a cochlear explant model, with the underlying mechanism involving both reactive oxygen species (ROS) suppression and STAT1 inhibition.

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Section: Discussionmentioning

confidence: 99%

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Jiang

Ray

Rybak³

et al. 2016

Otology &Amp; Neurotology

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“…Several biochemical pathways underlying these effects have been identified (e.g. : cardio-and neurovascular protection [5,6]; neuroprotection and anti-aging [7,8]). Studies dealing with the mechanisms of the bioactivity of resveratrol, the model polyphenol used in the present work, have been summarised in recent reviews [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Absorption and Metabolism of Resveratrol Carboxyesters and Methanesulfonate by Explanted Rat Intestinal Segments

Biasutto

Marotta

Mattarei

et al. 2009

Cell Physiol Biochem

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Model prodrugs of resveratrol carrying protecting substituents at the hydroxyls have been synthesised and tested. Resveratrol triacetate and resveratrol-tri-mPEG₁₉₀₀ were formed by linking methyl groups or poly(ethylene glycol) chains, respectively, via carboxyester bonds. Resveratrol trimesylate, a molecule less susceptible to hydrolytic attack, was synthesised as well. This latter compound proved to be stable in vitro, while the carboxyester derivatives were slowly hydrolysed in solutions mimicking the gastric or intestinal environment, and rapidly converted to resveratrol in blood. In ex vivo permeation experiments with explanted intestinal segments, resveratrol and its triacetate derivative appeared in the basolateral compartment essentially as a mixture of Phase II metabolites. When the PEGylated derivative was provided on the apical side, unconjugated resveratrol accounted for about 50% of the compounds in the basolateral-side chamber. The same result was obtained by providing an equivalent physical mixture of resveratrol and PEG polymer, indicating that this behaviour is likely due to an adjuvating effect of PEG rather than to the covalent polymer conjugation. These observations suggest that the ester derivatives are rapidly hydrolysed at the intestinal surface or inside enterocytes, and are then processed as resveratrol. On the other hand, the mesylate was transported from the apical to the basolateral side without modification. It may thus be possible to enhance absorption and hinder metabolism of natural polyphenols by constructing pro-drugs incorporating bonds with appropriate resistance to enzymatic hydrolysis.

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“…Epigallocatechin-3-gallate (EGCG) is an abundant polyphenol in green tea extract, which possesses antioxidant, anti-inflammatory and antitumorigenic properties, 22 , 23 , 24 , 25 , 26 and also a known inhibitor of STAT1. 21 , 27 Studies have shown beneficial effects of EGCG in treating diabetes, cancer, neurodegenerative disorders, cardiovascular disease and obesity. 28 , 29 , 30 , 31 Our interest in EGCG stems from the fact that it provides an orally effective STAT1 inhibitor with anticancer properties, which could complement the overall therapeutic benefits of cisplatin.…”

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confidence: 99%

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

et al. 2017

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Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy.

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Protective effect of epigallocatechin-3-gallate on ischemia/reperfusion-induced injuries in the heart: STAT1 silencing flavonoid

Cited by 16 publications

References 41 publications

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Absorption and Metabolism of Resveratrol Carboxyesters and Methanesulfonate by Explanted Rat Intestinal Segments

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

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