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Introduction: Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R., Materials and Methods: Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringle's maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min after reperfusion., Results: Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation., Conclusions: Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-kappaB and c-Jun signal transduction pathways.

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.

The aim of this study was to evaluate the effect of ( - )-epigallocatechin-3-gallate (EGCG), a natural antioxidant, on liver and lungs after warm intestinal ischemia/reperfusion (I/R). Thirty male Wistar rats were equally divided into a sham-operation group, an intestinal I/R group and an intestinal I/R group pretreated with EGCG intraperitoneally. Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 120 min. Immediately after reperfusion, liver, lung and blood samples were collected and analyzed. Results showed that intestinal I/R increased the levels of aspartate (AST) and alanine (ALT) transaminase in serum to 987 and 752 IU/l, respectively. Malondialdehyde (MDA) increased in liver to 1.524 nmol/g in the group subjected to intestinal I/R compared to 0.995 nmol/g in the sham operation group. MDA was also increased in lungs to 1.581 nmol/g compared to 0.896 nmol/g in the sham operation group. Myeloperoxidase (MPO) increased in liver, after intestinal I/R, to 5.16 U/g compared to 1.59 U/g in the sham operation group. MPO was also increased in lungs to 3.89 U/g compared to 1.65 U/g in the sham operation group. Pretreatment with EGCG decreased serum levels of AST and ALT to 236 and 178 IU/l, respectively. It also decreased mean MDA levels in liver and lungs to 1.061 and 1.008 nmol/g, respectively, and mean MPO levels in liver and lungs to 1.88 and 1.71 U/g, respectively. Light microscopy and transmission electron microscopy examinations showed significant alteration in liver and lungs and protection of liver and lung parenchyma in the animals treated with EGCG.

Purpose: To evaluate the combined effect of alpha-tocopherol and gadolinium chloride (GdCl3) in reducing lipid peroxidation after severe hepatic ischemia/reperfusion (IR) injury., Methods: Sixty male Wistar rats, 200-250 g, were randomly divided into six equal groups. There were two sham operation (SHAM) groups, two untreated IR groups, and two IR groups treated with GdCl3 and alpha-tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min reperfusion, one of each group was killed, liver samples were taken for malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy examination, and blood samples were analyzed for aspartate (AST) and alanine (ALT) transaminase, lactate dehydrogenase (LDH), and alpha-tocopherol content. The remaining groups were monitored for survival rate determination., Results: The mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were 1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The mean alpha-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were 10.4, 1.9, and 12 micromol/l. The mean serum AST, ALT, and LDH values were significantly higher in the IR group than in the SHAM group (P < 0.001), and significantly lower in the IRGT group than in the IR group (P < 0.001). Light microscopy examination revealed more severe congestion and vacuolization in the IR group than in the SHAM group, and minimal congestion and vacuolization in the IRGT group. Survival was significantly higher in the IRGT group than in the IR group., Conclusion: The administration of GdCl3 and alpha-tocopherol is likely to protect the liver against lipid peroxidation by suppressing Kupffer cell and polymorphonuclear leukocyte activation and enhancing endogenous antioxidant activity.

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.

Liver ischemia/reperfusion (I/R) results with severe oxidative stress. Enhanced production of reactive oxygen species, expression of inflammatory intermediates and their soluble receptors, triggers lipid peroxidation and cytosolic destruction in liver and in remote organs. The aim of our study was to evaluate the effect of epigallocatechin-3-gallate (EGCG) administration in lung and kidneys, in an experimental model of severe hepatic I/R. Administration of EGCG is likely to attenuate lipid peroxidation in lungs and kidneys and protect them from severe liver ischemia/reperfusion injury.

Hepatic ischemia and reperfusion results with severe oxidative stress, frequently overwhelming the endogenous antioxidant defense system. Enhanced production of reactive oxygen species, expression of inflammatory intermediates and nuclear factors trigger lipid peroxidation and cytosolic decomposition. The aim of this study was to evaluate the possible positive effect of epigallocatechin-3-gallate (EGCG) administration in an experimental model of severe hepatic ischemia/reperfusion and particularly the effect on lipid peroxidation. Preliminary result indicates that administration of EGCG is likely to attenuate lipid peroxidation and to protect liver from reperfusion injury.