Attenuation of Liver Ischemia/Reperfusion Induced Apoptosis by Epigallocatechin-3-Gallate Via Down-Regulation of NF-κB and c-Jun Expression

Giakoustidis, Dimitrios; Giakoustidis, Alexandros; Iliadis, Stavros; Koliakou, Kokona; Antoniadis, Nikolaos; Kontos, Nikolaos; Papanikolaou, Vasilios; Παπαγεωργίου, Γεώργιος; Kaldrimidou, E.; Takoudas, D

doi:10.1016/j.jss.2008.08.038

Cited by 49 publications

(37 citation statements)

References 53 publications

(66 reference statements)

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“…Reperfusion of the ischemic liver has been reported to activate Kupffer cells, increase the release of TNF-α, trigger apoptotic genes, activate caspase and cause degradation, leading to the emergence of DNA fragments and apoptotic bodies (24). Previous investigators have documented that liver endotheliocyte damage, microvascular dysfunction and the activation of Kupffer cells are involved in caspase-mediated apoptosis (25)(26)(27). These observations provide an explanation for the results of the present study.…”

Section: Discussionsupporting

confidence: 81%

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Meng

Yuan

Wei

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-βII activation and the role of PKC-β inhibitors are well understood in myocardial I/R in diabetes, they remain unclear in liver I/R. The aim of this study was to explore the effect of PKC-β inhibition and the potential mechanism by which PKC-β inhibitor treatment protects against hepatic I/R injury in diabetic rats. Diabetic rats were established and randomized into two groups. These were an untreated group (n=10), which did not receive any treatment, and a treatment group (n=10), orally treated with ruboxistaurin at a dose of 5 mg/kg/day for 2 weeks. The rats from the two groups were subjected to hepatic I/R. Aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels were measured by enzymatic methods at 1, 3 and 5 h after I/R. Tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) were examined by enzyme-linked immunosorbent assay at the same time-points. Nuclear factor-κB (NF-κB) p65 expression was analyzed by immunofluorescence and western blotting. Apoptosis of hepatic cells was examined by the western blot analysis of caspase 3 expression and by DNA ladder analysis. Pathological changes were examined using light and electron microscopy. Serum AST and LDH levels in the PKC-β inhibitor treatment group were diminished compared with those in the untreated group (P<0.01). Serum TNF-α and ICAM-1 (P<0.01) levels were also decreased at different time-points in the PKC-β inhibitor treatment group. The relative expression of NF-κB p65 and caspase 3 in the hepatic tissue was weakened in the PKC-β inhibitor treatment group compared with that in the untreated group (P<0.01). Pathological changes in hepatic tissue were attenuated by the PKC-β inhibitor. In conclusion, PKC-β inhibitor treatment protected against liver I/R injury in diabetic rats. The mechanisms probably involved the attenuation of microvascular injury, reduced transport of injury-associated factors and diminishment of the activation of NF-κB p65.

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Section: Discussionsupporting

confidence: 81%

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Meng

Yuan

Wei

et al. 2015

Experimental and Therapeutic Medicine

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“…All liver samples were analysed on the same day. MPO activity was measured according to the method described by Giakoustidis et al 24 Briefly, liver tissue homogenates are treated with hexadecyltrimethylammonia to release MPO from the granules in neutrophils, and the supernatant is analysed spectrophotometrically after adding tetramethylbenzidin and H 2 O 2 by measuring absorption ad 655 nm for 60 s at 25 1C. Results are expressed as U MPO/g liver tissue.…”

Section: Myeloperoxidase Activitymentioning

confidence: 99%

Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture

Francque

Laleman²,

Verbeke³

et al. 2012

Laboratory Investigation

106

124

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Non-alcoholic fatty liver disease can progress to steatohepatitis and fibrosis, and is also associated with impaired liver regeneration. The pathophysiology remains elusive. We recently showed that severe steatosis is associated with an increase in portal pressure, suggesting liver flow impairment. The objective of this study is to directly assess total intrahepatic resistance and its potential functional and structural determinants in an in situ perfusion model. Male Wistar rats fed a control (n ¼ 30) or a methionine-choline-deficient (MCD) diet (n ¼ 30) for 4 weeks were compared. Liver tissue and serum analysis, in vivo haemodynamic measurements, in situ perfusion experiments and vascular corrosion casts were performed. The MCD group showed severe steatosis without inflammation or fibrosis on histology. Serum levels and liver tissue gene expression of interleukin (IL)-6, tumour necrosis factor-a, IL-1b and interferon-g, liver tissue myeloperoxidase activity and liver immunohistochemistry with anti-CD68 and anti-a smooth muscle actin were comparable between groups, excluding significant inflammation. Flow-pressure curves were significantly different between groups for all flows (slope values: 0.1636±0.0605 mm Hg/ml/min in controls vs 0.7270±0.0408 mm Hg/ml/min in MCD-fed rats, Po0.001), indicating an increased intrahepatic resistance, which was haemodynamically significant (portocaval pressure gradient 2.2 ± 1.1 vs 8.2 ± 1.3 mm Hg in controls vs MCD, Po0.001). Dose-response curves to acetylcholine were significantly reduced in MCD-fed rats (Po0.001) as was the responsiveness to methoxamine (Po0.001). Vascular corrosion casts showed a replacement of the regular sinusoidal anatomy by a disorganized pattern with multiple interconnections and vascular extensions. Liver phosphorylated endothelial NO synthase (eNOS)/eNOS and serum nitrite/nitrate were not increased in severe steatosis, whereas liver thromboxane synthase expression, liver endothelin-1 (ET-1) expression and serum andothelin-1 concentration were significantly increased. Severe steatosis induces a haemodynamically significant increase in intrahepatic resistance, which precedes inflammation and fibrogenesis. Both functional (endothelial dysfunction and increased thromboxane and ET-1 synthesis) and structural factors are involved. This phenomenon might significantly contribute to steatosis-related disease.

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“…These anti-inflammatory effects of EGCG are supported by previous studies. In 2 separate studies, Giakoustidis et al demonstrated EGCG's protective effects against ischemia-reperfusion injury to the liver and intestine by downregulating c-Jun and NF-kappaB [34,35]. Townsend et al carried out an experimental study on cell cultures prepared from the rat's myocardium.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of Epigallocatechin Gallate Against Distant Organ Damage After Severe Skin Burns – Experimental Study Using a Rat Model of Thermal Trauma

Hoşnuter¹,

Melikoglu²,

Aslan³

et al. 2015

Adv Clin Exp Med

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Background. Epigallocatechin gallate (EGCG), a green tea polyphenol, has potent antioxidant properties. Objectives. The purpose of the present study was to examine the possible preventative effects of EGCG against internal organ injury due to large-surface skin burns in a rat model. Material and Methods. The study design involved three groups of rats: a sham group and two groups with 25-30% full-thickness burns: (a) the sham group without burns or treatment (n = 18); (b) the control burn group (burns + sterile saline, n = 18); and (c) the burn treatment group (burns + treatment with EGCG, n = 18). EGCG was administered intraperitoneally immediately after the thermal injury, and daily in 100 μmol/kg doses. Kidney and lung tissue samples were taken to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and glutathione peroxidase (GPX) after the first, third and seventh post-burn days. Results. In the EGCG-treated burn group, SOD and GPX activity were significantly higher than in the burn control group. Additionally, MDA and TNF-α levels were significantly lower in the EGCG-treated burn group. Conclusions. Based on this study, it might be anticipated that EGCG treatment may be beneficial in burn injury cases (Adv Clin Exp Med 2015, 24, 3, 409-417).

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Attenuation of Liver Ischemia/Reperfusion Induced Apoptosis by Epigallocatechin-3-Gallate Via Down-Regulation of NF-κB and c-Jun Expression

Cited by 49 publications

References 53 publications

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture

The Protective Effects of Epigallocatechin Gallate Against Distant Organ Damage After Severe Skin Burns – Experimental Study Using a Rat Model of Thermal Trauma

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