Biomedical subjects

Basilia Zingarelli

Publications and source records attributed to Basilia Zingarelli.

32 records · Page 2Linked to original sources

PubMed2003

Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1.

Poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme activated in response to DNA strand breaks, has been implicated in cell dysfunction in myocardial reperfusion injury. PARP-1 has also been shown to participate in transcription and regulation of gene expression. In this study, we investigated the role of PARP-1 on the signal transduction pathway of activator protein-1 (AP-1) and heat shock factor-1 (HSF-1) in myocardial reperfusion injury. Mice genetically deficient of PARP-1 (PARP-1(-/-) mice) exhibited a significant reduction of myocardial damage after occlusion and reperfusion of the left anterior descending branch of the coronary artery compared with their wild-type littermates. This cardioprotection was associated with a reduction of the phosphorylative activity of JNK and, subsequently, reduction of the DNA binding of the signal transduction factor AP-1. On the contrary, in PARP-1(-/-) mice, DNA binding of HSF-1 was enhanced and was associated with a significant increase of the cardioprotective heat shock protein (HSP)70 compared with wild-type mice. Microarray analysis revealed that expression of several AP-1-dependent genes of proinflammatory mediators and HSPs was altered in PARP-1(-/-) mice. The data indicate that PARP-1 may exert a pathological role in reperfusion injury by functioning as an enhancing factor of AP-1 activation and as a repressing factor of HSF-1 activation and HSP70 expression.

Animals↗

PubMed2003

Inhibitors of poly (ADP-ribose) polymerase modulate signal transduction pathways in colitis.

During inflammatory bowel diseases, oxidative and nitrosative stress induces DNA damage and activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), resulting in depletion of intracellular energetics, intestinal barrier dysfunction and cellular death. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in experimental colitis, which was induced by rectal instillation of trinitrobenzene sulfonic acid (TNBS) in rats. In vehicle-treated rats, TNBS treatment resulted in colonic erosion and ulceration. Neutrophil infiltration (indicated by myeloperoxidase activity in the colon) was associated with formation of nitrotyrosine and marked apoptosis. Elevated levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also found. These inflammatory events were associated with the activation of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) in the colon; NF-kappa B was maximally activated at 3 and 7 days, whereas AP-1 increased 1 day after TNBS administration and declined thereafter. Treatment of the rats with the PARP inhibitors, 3-aminobenzamide or 1,5-dihydroxyisoquinoline, resolved colonic damage and reduced plasma levels of NO metabolites. Resolution of the damage was associated with reduction of neutrophil infiltration, nitrotyrosine formation and apoptosis. Treatment with PARP inhibitors also reduced DNA binding of NF-kappa B and AP-1 in the colon. These data demonstrate that pharmacological inhibition of PARP ameliorates colitis. Reduction of the inflammatory process is associated with modification of the activation of signal transduction pathways.

Animals↗

PubMed2003

Poly(ADP-ribose) polymerase-1 regulates activation of activator protein-1 in murine fibroblasts.

Poly(ADP-ribose) polymerase (PARP)-1 is activated in response to DNA injury in the nucleus of eukaryotic cells and has been implicated in cell dysfunction in inflammation. We investigated the role of PARP-1 on the AP-1 pathway, which is involved in the signal transduction of the inflammatory process. In murine wild-type fibroblasts, oxidative challenge by peroxynitrite and hydrogen peroxide or immunological challenge by IL-1 and 20% FCS induced phosphorylation of the mitogen-activated protein kinase kinase-4, activation of c-Jun N-terminal kinase (JNK), and DNA binding of AP-1. In comparative experiments, peroxynitrite induced DNA binding of heat shock factor-1. Pretreatment of wild-type cells with 5-iodo-6-amino-1,2-benzopyrone, a PARP-1 inhibitor, inhibited JNK activation and DNA binding of AP-1. In parallel experiments in PARP-1-deficient fibroblasts, DNA binding of AP-1 was completely abolished. Activation of JNK was significantly elevated at basal condition, but it exhibited a lesser increase after oxidative or immunological challenge than in wild-type fibroblasts. Nuclear content of phosphorylated mitogen-activated protein kinase kinase-4 was observed in PARP-1-deficient cells after peroxynitrite challenge only. Western blotting analysis for AP-1 subunits indicated that c-Fos was similarly expressed in wild-type and PARP-1-deficient cells. Phosphorylated c-Jun was expressed after oxidative or immunological challenge, but not in basal condition, in wild-type cells; however, it was significantly elevated at basal condition and further enhanced after oxidative or immunological challenge in PARP-1-deficient cells. No DNA binding of heat shock factor-1 was observed in PARP-1-deficient cells. These data demonstrate that PARP-1 plays a pivotal role in the modulation of transcription.

Animals↗

PubMed2003

Nuclear factor-kappaB as a therapeutic target in critical care medicine.

Nuclear factor-kappaB is a transcriptional factor required for the gene expression of many inflammatory mediators. Nuclear factor-kappaB activation requires removal and degradation of its inhibitor kappaB, an event that occurs after phosphorylation of inhibitor kappaB by a complex of inhibitor kappaB kinases. These events allow nuclear factor-kappaB to translocate into the nucleus, where it binds to kappaB elements and initiates transcription. Inappropriate and prolonged activation of nuclear factor-kappaB has been linked to several diseases associated with inflammatory events, including septic shock, acute respiratory distress syndrome, ischemia, and reperfusion injury. Thus, the key role of nuclear factor-kappaB in regulating inflammation makes this factor a therapeutic target for reducing tissue and organ damage. Regulation and control of nuclear factor-kappaB can be achieved by gene modification strategies or by pharmacologic inhibition of the key components of the cascade that leads to nuclear factor-kappaB activation. The purpose of our review is to describe these novel therapeutic approaches and their potential efficacy.

Critical Care↗

PubMed2003

Parthenolide improves systemic hemodynamics and decreases tissue leukosequestration in rats with polymicrobial sepsis.

OBJECTIVE: Nuclear factor (NF)-kappaB is a transcriptional factor required for the gene expression of many inflammatory mediators. This study was designed to investigate the biological effects of parthenolide, a specific inhibitor of NF-kappaB activation, in experimental sepsis and multiple organ failure. DESIGN: Prospective, randomized laboratory investigation that used an established model of cecal ligation and puncture to induce polymicrobial sepsis in rats. SETTING: University hospital laboratory. SUBJECTS: Male Sprague Dawley rats underwent cecal ligation and puncture followed by the administration of saline solution. INTERVENTIONS: A group of rats received parthenolide (1 mg/kg) intraperitoneally. Mean arterial blood pressure was monitored for 18 hrs, and survival rate was monitored for 4 days. In a separate experiment, rats were killed at 1, 3, 6, and 18 hrs after cecal ligation and puncture. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated animals, cecal ligation and puncture resulted in polymicrobial sepsis and was associated with 20% mortality rate, marked hypotension, and lung injury. Immunohistochemistry showed positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) in thoracic aortas. There was a significant increase in plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-10. Elevated levels of myeloperoxidase activity in lung, colon, and liver were indicative of infiltration of neutrophils. These inflammatory events were associated with activation of NF-kappaB in the lung in a time-dependent fashion. In vivo treatment with parthenolide improved the hemodynamic profile and survival; reduced neutrophil infiltration in lung, colon, and liver; and reduced plasma concentrations of cytokines. Treatment with parthenolide also abolished formation of nitrotyrosine and expression of PARP-1 in thoracic aortas. These beneficial effects of parthenolide were associated with reduction of NF-kappaB activity in the lung. CONCLUSIONS: Our data suggest that pharmacologic inhibition of NF-kappaB may represent a potential therapeutic approach in sepsis.

Animals↗

PubMed2003

Peroxisome proliferator-activated receptor-gamma agonists modulate macrophage activation by gram-negative and gram-positive bacterial stimuli.

Bacterial products, such as lipopolysaccharide (LPS) or heat-killed Escherichia coli (EC), and heat-killed Staphylococcus aureus (SA) are potent activators of macrophages (MØ). When stimulated by these bacterial components, MØ produce inflammatory mediators, such as nitric oxide (NO) and thromboxane (Tx) B(2). Bacterial mediator production is preceded by the activation of various signal transduction pathways. Agonists that activate the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been shown to block MØ mediator production by LPS and other stimuli. However, very little is known about the effects of PPARgamma agonists on SA- or EC-induced MØ activation. Therefore, we investigated whether the PPARgamma agonists 15-deoxy-Delta12,14 prostaglandin J(2) (15-PGJ(2)) and troglitazone block LPS-, EC-, or SA-induced mediator production. Rat peritoneal MØ were stimulated with LPS, EC, or SA (10 microg/mL) with or without increasing concentrations (0.1 to 10 microM) of each PPARgamma agonist and NO and TxB(2) production were measured. 15-PGJ(2) decreased LPS-, EC-, and SA-induced NO and TxB(2) production. However, troglitazone only inhibited the production of TxB(2) by each stimuli. In parallel studies, the effects of PPARgamma agonists on signaling pathways were evaluated. Rat peritoneal MØ were pretreated for 1 h with 15-PGJ(2) or troglitazone (1 or 10 microM) and then stimulated for 40 min with LPS, EC, or SA (10 microg/mL). Western blot analysis demonstrated that 15-PGJ(2) significantly inhibited LPS-, EC-, and SA-induced ERK (1/2) activation and blocked IkappaBalpha degradation. Troglitazone had no significant effect on either signaling protein. The data demonstrate that although both 15-PGJ(2) and troglitazone are considered PPARgamma agonists, they differentially affect mediator production and cell signaling events. PPARgamma-independent effects of 15-PGJ(2) may contribute to its more potent anti-inflammatory effects compared with troglitazone.

Animals↗

PubMed2003

Inhibition of nitric oxide restores surfactant gene expression following nickel-induced acute lung injury.

The role of nitric oxide (NO) in acute lung injury remains controversial. Although inhaled NO increases oxygenation in clinical trials, inhibiting NO-synthase (NOS) can be protective. To examine the latter, nickel-exposed mice were treated with saline or NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). Initial microarray analysis of nickel-induced gene expression of saline-treated mice revealed increased inflammatory mediator, matrix injury-repair, and hypoxia-induced factor-mediated sequences and decreased lung-specific (e.g., surfactant-associated protein B and C) sequences. Compared with saline control, L-NAME-treated mice had enhanced survival with attenuated serum nitrate/nitrite, endothelial NOS activity, and lavage neutrophils and protein. Although initial cytokine (i.e., interferon-gamma, interleukins-1beta and -6, macrophage inflammatory protein-2, monocyte chemotactic protein-1, and tumor necrosis factor-alpha) gene expression was similar between groups, subsequent larger cytokine increases only occurred in saline-treated mice. Similarly, surfactant protein gene expression decreased initially in both groups yet was restored subsequently with L-NAME treatment. Interestingly, the role of inducible NOS (iNOS) in these responses seems minimal. iNOS gene expression was unaltered, iNOS activity and nitrotyrosine residues were undetectable, and an iNOS antagonist, aminoguanidine, failed to increase survival. Rather, systemic L-NAME treatment appears to attenuate pulmonary endothelial NOS activity, subsequent cytokine expression, inflammation, and protein permeability, and thereby restores surfactant gene expression and increases survival.

Animals↗

PubMed2002

Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damage.

The role of nitric oxide (NO) generated by the inducible NO synthase (iNOS) during myocardial ischemia and reperfusion is not understood. We investigated the role of iNOS during early reperfusion damage induced in genetically deficient iNOS (iNOS-/-) mice and wild-type littermates. In wild-type mice, ischemia (60 min) and reperfusion (60 min) induced an elevation in serum levels of creatine phosphokinase and myocardial injury characterized by the presence of scattered apoptotic myocytes and mild neutrophil infiltration. Northern blot analysis showed increased expression of iNOS, whose activity was markedly elevated after reperfusion. Immunohistochemistry showed staining for nitrotyrosine; Western blot analysis showed elevated expression of heat shock protein 70 (HSP70), a putative cardioprotective mediator. Plasma levels of nitrite and nitrate, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-10 were also increased. These events were preceded by degradation of inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex (IKK) and c-Jun-NH2-terminal kinase (JNK), and subsequently activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) as early as 15 min after reperfusion. In contrast, iNOS-/- mice experienced 35% mortality after reperfusion. The extensive myocardial injury was associated with marked apoptosis and infiltration of neutrophils whereas expression of HSP70 was less pronounced. Nitrotyrosine formation and plasma levels of nitrite and nitrate were undetectable. TNF-alpha and IL-6 were increased and IL-10 was reduced in earlier stages of reperfusion. Activation of IKK and JNK and binding activity of NF-kappaB and AP-1 were significantly reduced. Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction.

Animals↗

PubMed2002

Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis.

OBJECTIVE: This study was designed to evaluate the use of moderate hypothermia in a model of meningitis-induced brain injury and its effect on the activation of nuclear factor-kappaB, biological markers of neuronal injury, and neurobehavioral performance. DESIGN: Randomized, prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern tap receiving either sterile saline as a placebo or an equivalent volume of a group B streptococcal suspension. Sixteen hours after inoculation, animals were stratified by their clinical severity score, were randomized to either hypothermic (32-34 degrees C) or normothermic (37-39 degrees C) conditions, and received antibiotics. Hypothermic animals were kept under these temperature conditions for 6 hrs before rewarming. Two protocols were used. For the first protocol, changes in nuclear factor-kappaB activation and heat shock protein induction at 24 hrs and 48 hrs after inoculation were evaluated. In the second protocol, serum C-tau concentrations at 5 days and neurobehavioral performances at 3 wks were assessed. MEASUREMENTS AND MAIN RESULTS: Meningitis triggered a >50% increase in cerebral nuclear factor-kappaB activation. The addition of a 6-hr period of hypothermia reduced nuclear factor-kappaB activation by 32% when measured at the end of the hypothermic period. At 48 hrs, this decrease in nuclear factor-kappaB activation was no longer apparent, but there was a significant decrease in the heat shock response. Serum C-tau concentrations at 5 days postinjury, a biomarker of brain injury, were reduced by 69% in hypothermic treated animals. Furthermore, hypothermia reduced the brain water content of infected animals. However, hypothermia did not improve the animals' neurobehavioral performance. CONCLUSION: The findings from this study suggest that hypothermia produces a transitory attenuation of nuclear factor-kappaB activation in meningitic brain injury and improvement in some biomarkers of neuronal injury. The consequence of intermittent suppression of nuclear factor-kappaB activation by inducing specific periods of hypothermia requires further study.

Analysis of Variance↗

PubMed2002

Sesquiterpene lactone parthenolide, an inhibitor of IkappaB kinase complex and nuclear factor-kappaB, exerts beneficial effects in myocardial reperfusion injury.

Sesquiterpene lactones are extracts of common medicinal Asteracae plants used in folk medicine for their anti-inflammatory activity. Recently, in vitro studies have shown that these compounds may interfere with pro-inflammatory gene regulation. This study examines the effects of parthenolide, a sesquiterpene lactone, in experimental myocardial ischemia and reperfusion. Myocardial injury was induced in rats by 30 min occlusion and 120 min reperfusion of the left coronary artery. Parthenolide (250 or 500 microg/kg) or vehicle (0.05% Tween 80, 1 mL/kg) was administered intraperitoneally 10 min before reperfusion. In vehicle-treated rats, ischemia and reperfusion caused myocardial injury, as evaluated by infarct size, serum levels of creatine phosphokinase and by histological examination. Elevated tissue levels of myeloperoxidase activity were indicative of a significant infiltration of neutrophils. This event paralleled the occurrence of oxidative damage, as evaluated by a marked increase in tissue malondialdehyde levels. These inflammatory events were preceded by activation of the IkappaB kinase complex (IKK) and partial disappearance of inhibitor-kappaBalpha (IkappaBalpha) in the cytosol and translocation of the nuclear factor-kappaB (NF-kappaB) to the nucleus, as early as 15 min after reperfusion. Administration of parthenolide ameliorated myocardial injury, lowered serum creatine phosphokinase activity, and reduced neutrophil infiltration and the subsequent oxidative damage. These beneficial effects were associated with inhibition of IKK activity, enhanced stability of IkappaBalpha, and inhibition of nuclear translocation of NF-kappaB. The results of this study suggest that parthenolide may be beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the IKK/NF-kappaB pathway.

Animals↗

PubMed2002

Inducible nitric oxide synthase is not required in the development of endotoxin tolerance in mice.

We investigated the role of inducible nitric oxide synthase (iNOS) in endotoxin tolerance, which was induced in mice genetically deficient of iNOS (iNOS-/-) and in wild-type littermates. In non-tolerant wild-type mice, endotoxin induced high mortality, elevation of plasma levels of nitrite and nitrate, tumor necrosis factor a (TNFalpha), and interleukin 10 (IL-10). These events were preceded by degradation of inhibitors kappaBalpha (IkappaBalpha) and kappaBI (IkappaBbeta), and activation of nuclear factor-kappaB (NF-kappaB) in the lung. Pretreatment of wild-type mice with a sublethal dose of endotoxin prior to lethal endotoxin administration ameliorated lethality and blunted TNFalpha production, whereas IL-10, nitrite, and nitrate production was maintained. These events were associated with reduction of IKBa degradation and NF-kappaB activation in the lung. The kinetics of degradation of IkappaBbeta were also altered. In parallel experiments, nontolerant iNOS-/- mice experienced similar mortality after endotoxin as nontolerant wild-type mice. Plasma levels of nitrite and nitrate were not elevated after lethal endotoxin administration. IL-10 levels were significantly reduced in comparison to nontolerant wild-type mice, whereas TNFalpha levels were similarly increased. These events were preceded by lesser degradation of IkappaBalpha and reduced NF-kappaB activation in the lung. Pretreatment of iNOS-/- mice with a sublethal endotoxin ameliorated lethality. TNFalpha production was significantly reduced, whereas IL-10 production was significantly increased when compared to nontolerant iNOS-/- mice. Degradation of IkappaBalpha and activation of NF-kappaB in the lung were not altered by endotoxin tolerance, whereas kinetics of IkappaBbeta degradation was only delayed. Our data suggests that iNOS is not required for the development of endotoxin tolerance, and that other signal transduction pathways, rather than NF-kappaB, may regulate induction of endotoxin tolerance in the absence of iNOS.

Animals↗

PubMed2002

Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents.

Parthenolide is a sesquiterpene lactone used in folk medicine for its anti-inflammatory activity. Recent in vitro studies have shown that this compound inhibits the nuclear factor (NF)-kappaB pathway. This study examines the effect of parthenolide in endotoxic shock in rodents. Endotoxic shock was induced by administration of Escherichia coli endotoxin in rats. Three groups of rats received parthenolide (0.25, 0.5, or 1 mg/kg) 15 min before endotoxin; another group received parthenolide (1 mg/kg) 3 h after endotoxin. In vehicle-treated rats, administration of endotoxin caused severe hypotension, which was associated with a marked hyporeactivity to norepinephrine in ex vivo thoracic aortas. Immunohistochemistry showed positive staining for nitrotyrosine, poly(ADP-ribose) synthetase (PARS) and apoptosis, whereas Northern blot analysis showed increased mRNA expression of inducible nitric-oxide synthase (iNOS) in thoracic aortas. Elevated levels of plasma nitrate/nitrite were also found. Elevated lung levels of myeloperoxidase activity were indicative of infiltration of neutrophils. These inflammatory events were preceded by cytosolic degradation of inhibitor kappaBalpha (IkappaBalpha) and activation of nuclear NF-kappaB in the lung. In vivo pretreatment and post-treatment with parthenolide improved the hemodynamic profile and reduced plasma nitrate/nitrite and lung neutrophil infiltration in a dose-dependent fashion. Vascular hyporeactivity of ex vivo aortas was ameliorated. Treatment with parthenolide also abolished nitrotyrosine formation, PARS expression, and apoptosis and reduced iNOS mRNA content in thoracic aortas. DNA binding of NF-kappaB was inhibited by parthenolide in the lung, whereas degradation of IkappaBalpha was unchanged. In a separate set of experiments, pretreatment or post-treatment with parthenolide significantly improved survival in mice challenged with endotoxin. We conclude that parthenolide exerts beneficial effects during endotoxic shock through inhibition of NF-kappaB.

Animals↗

PubMedDate not supplied

Absence of poly(ADP-ribose)polymerase-1 alters nuclear factor-kappa B activation and gene expression of apoptosis regulators after reperfusion injury.

Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in eukaryotic cells and has been implicated in cell dysfunction in reperfusion injury. In this study we investigated the role of PARP-1 on apoptosis in early myocardial reperfusion injury. Mice genetically deficient of PARP-1 (PARP-1-/-) and wild-type littermates were subjected to myocardial ischemia and reperfusion. Myocardial injury was assessed by measuring the serum levels of creatine phosphokinase and oligonucleosomal DNA fragments in the infarcted area. Expression of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax, was analyzed by Western blot. Activation of caspases, important executioners of apoptosis, and activation of the nuclear factor kappa B (NF-kappa B) pathway were evaluated. Gene expression profiles for apoptotic regulators between PARP-1-/- and wild-type mice also were compared. Myocardial damage in PARP-1-/- mice was reduced significantly, as indicated by lower serum creatine phosphokinase levels and reduction of apoptosis, as compared with wild-type mice. Western blot analyses showed increased expression of Bcl-2, which was associated with reduction of caspase-1 and caspase-3 activation. This cardioprotection was associated with significant reduction of the activation of I kappa B kinase complex and NF-kappa B DNA binding. Microarray analysis demonstrated that the expression of 29 known genes of apoptotic regulators was significantly altered in PARP-1-/- mice compared with wild-type mice, whereas 6 known genes were similarly expressed in both genotypes. The data indicate that during reperfusion absence of PARP-1 leads to reduction of myocardial apoptosis, which is associated with reduced NF-kappa B activation and altered gene expression profiles.

Animals↗

PubMedDate not supplied

Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats.

Epigallocatechin-3-gallate (EGCG) is the most prominent catechin in green tea. EGCG has been shown to modulate numerous molecular targets in the setting of inflammation and cancer. These molecular targets have also been demonstrated to be important participants in reperfusion injury, hence this study examines the effects of EGCG in myocardial reperfusion injury. Male Wistar rats were subjected to myocardial ischemia (30 min) and reperfusion (up to 2 h). Rats were treated with EGCG (10 mg/kg intravenously) or with vehicle at the end of the ischemia period followed by a continuous infusion (EGCG 10 mg/kg/h) during the reperfusion period. In vehicle-treated rats, extensive myocardial injury was associated with tissue neutrophil infiltration as evaluated by myeloperoxidase activity, and elevated levels of plasma creatine phosphokinase. Vehicle-treated rats also demonstrated increased plasma levels of interleukin-6. These events were associated with cytosol degradation of inhibitor kappaB-alpha, activation of IkappaB kinase, phosphorylation of c-Jun, and subsequent activation of nuclear factor-kappaB and activator protein-1 in the infarcted heart. In vivo treatment with EGCG reduced myocardial damage and myeloperoxidase activity. Plasma IL-6 and creatine phosphokinase levels were decreased after EGCG administration. This beneficial effect of EGCG was associated with reduction of nuclear factor-kB and activator protein-1 DNA binding. The results of this study suggest that EGCG is beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the NF-kappaB and AP-1 pathway.

Animals↗