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Bela Juhasz,
Attila Kertész,
Jozsef Balla,
Gyorgy Balla,
Zoltán Szabo,
Mariann Bombicz,
Daniel Priksz,
Rudolf Gesztelyi,
Balazs Varga,
David D Haines,
Arpad Tosaki
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ABSTRACT: Hypothesis. The present study evaluates the hypothesis that sour cherry seed extract (SCSE) protects against cardiovascular disease and inflammation in hypercholesterolemic rabbits, and that this protection correlates with SCSE-induced activity of heme oxygenase-1 (HO-1), a cytoprotective enzyme contributing to oxidative stress responses. Methods: 18 New Zealand white rabbits were divided into three groups receiving: I. cholesterol-free rabbit chow; II. chow containing 2% cholesterol; or III. 2% cholesterol plus SCSE for 16 weeks. Heart functions were monitored by echocardiography 0, 4, and 16 weeks after the initiation of cholesterol-supplemented feeding. At the 16-week time-point, isolated hearts were subjected to ischemia-reperfusion (I/R), followed by measurement of heart rate (HR), aortic flow (AF), coronary flow (CF), aortic pressure (AoP), and left ventricular developed pressure (LVDP). Myocardial infarct size was determined using triphenyl tetrazolium chloride (TTC). Quantification of fatty streaks was assessed using Sudan-III staining. Western blot analysis was used to determine the content of cytochrome c oxidase III (COX III), vascular endothelial growth factor (VEGF), and HO-1 in the myocardium. Results: Relative to cholesterol-treated animals not receiving SCSE, SCSE-treated animals exhibited significantly improved cardiac function and improved peak early diastolic velocity to peak atrial velocity ratio (E'/A'), along with decreased the atherosclerotic plaque formation and infarct size. Increased HO-1 and COX III protein expression and COX activity were also noted in hearts from SCSE-treated rabbits. Conclusions: This study demonstrates SCSE cardioprotective effects on hypercholesterolemic hearts. Correlation of these outcomes with HO-1 expression suggests that the effect may be mediated by activity of this enzyme. However, definitive proof of HO-1 dependence requires further investigation.
Current pharmaceutical design 04/2013; · 4.41 Impact Factor
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ABSTRACT: The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism-and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.
Journal of Molecular Neuroscience 03/2013; · 2.50 Impact Factor
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Rudolf Gesztelyi,
Zsuzsanna Kiss,
Zita Wachal, Bela Juhasz,
Mariann Bombicz,
Evelin Csepanyi,
Krisztian Pak,
Judit Zsuga,
Csaba Papp,
Zoltan Galajda,
Klara Branzaniuc,
Robert Porszasz,
Andras Jozsef Szentmiklosi,
Arpad Tosaki
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ABSTRACT: A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.
Archives of Pharmacal Research 02/2013; · 1.59 Impact Factor
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ABSTRACT: Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2012; 51C:26-32. · 2.99 Impact Factor
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ABSTRACT: Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2(-/-) mice. Both wild-type (WT) and Nox2(-/-) mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dt (max) (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2(-/-)IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2(-/-) IPIR hearts. Selected differentially regulated genes such as β-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2(-/-) mice by using microarray analysis.
Functional & Integrative Genomics 10/2011; 12(3):501-14. · 3.83 Impact Factor
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Bela Juhasz,
Balazs Varga,
Attila Czompa,
Istvan Bak,
Istvan Lekli,
Rudolf Gesztelyi,
Judit Zsuga,
Adam Kemeny-Beke,
Miklos Antal,
Levente Szendrei,
Arpad Tosaki
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ABSTRACT: Heme oxygenase-1 (HO-1) transgenic mice (Tg) were created using a rat HO-1 genomic transgene. Transgene expression was detected by RT-PCR and Western blots in the left ventricle (LV), right ventricle (RV) and septum (S) in mouse hearts, and its function was demonstrated by the elevated HO enzyme activity. Tg and non-transgenic (NTg) mouse hearts were isolated and subjected to ischemia/reperfusion. Significant post-ischemic recovery in coronary flow (CF), aortic flow (AF), aortic pressure (AOP) and first derivative of AOP (AOPdp/dt) were detected in the HO-1 Tg group compared to the NTg values. In HO-1 Tg hearts treated with 50 μmol/kg of tin protoporphyrin IX (SnPPIX), an HO enzyme inhibitor, abolished the post-ischemic cardiac recovery. HO-1 related carbon monoxide (CO) production was detected in NTg, HO-1 Tg and HO-1 Tg + SnPPIX treated groups, and a substantial increase in CO production was observed in the HO-1 Tg hearts subjected to ischemia/reperfusion. Moreover, in ischemia/reperfusion-induced tissue Na(+) and Ca(2+) gains were reduced in HO-1 Tg group in comparison with the NTg and HO-1 Tg + SnPPIX treated groups; furthermore K(+) loss was reduced in the HO-1 Tg group. The infarct size was markedly reduced from its NTg control value of 37 ± 4% to 20 ± 6% (P < 0.05) in the HO-1 Tg group, and was increased to 47 ± 5% (P < 0.05) in the HO-1 knockout (KO) hearts. Parallel to the infarct size reduction, the incidence of total and sustained ventricular fibrillation were also reduced from their NTg control values of 92% and 83% to 25% (P < 0.05) and 8% (P < 0.05) in the HO-1 Tg group, and were increased to 100% and 100% in HO-1 KO(-/-) hearts. Immunohistochemical staining of HO-1 was intensified in HO-1 Tg compared to the NTg myocardium. Thus, the HO-1 Tg mouse model suggests a valuable therapeutic approach in the treatment of ischemic myocardium.
Journal of Cellular and Molecular Medicine 09/2011; 15(9):1973-82. · 4.13 Impact Factor
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ABSTRACT: The present report describes outcomes of animal studies conducted to determine the systemic and dermal toxicity of Prunus cerasus (sour cherry) seed kernel contents; and a separate evaluation of the photoprotective capacity of the kernel oil fraction. B6 mice and Hartley guinea-pigs were used for these experiments. Dosage groups of 6-8 animals were administered whole kernel meal in a dose range of 0-3000 mg/kg by gavage for 8 days, following which they were killed. The liver and kidney weights were recorded and histological examination performed on sections of these organs. Kidney function was assessed as blood urea nitrogen and creatinine and liver function by measurement of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase. Dermal toxicity was evaluated in a Hartley guinea-pig model by comparing UVB-irradiated shaved skin to which the kernel oil had been applied with distilled water controls. In conclusion, no evidence of toxicity was observed to result from the consumption or dermal application of sour cherry seed kernel in the dose range at which it is likely to be used in foods or healthcare. Moreover, it was shown to have a powerful capacity to protect skin from UV damage. These results suggest it will prove to be a highly safe and effective addition to a wide range of products for general use.
Phytotherapy Research 07/2011; 25(11):1714-20. · 2.09 Impact Factor
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ABSTRACT: This study tested the hypothesis that the induction of autophagy by producing therapeutic amounts of endoplasmic reticulum (ER) stress in the heart before an ischemic insult would ameliorate/reduce subsequent lethal myocardial ischemic/reperfusion (I/R) injury (similar to ischemic preconditioning). A dose-response study with both tunicamycin and thapsigargin was performed to determine the optimal dose (0.3 mg/kg) for inducing autophagy for cardioprotection. The Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned into five groups: normal control (injected with saline only), high (3 mg/kg), and low (0.3 mg/kg) doses of tunicamycin or thapsigargin, respectively. After 48 h, the rats were subjected to an isolated working heart preparation: 30 min ischemia followed by 2 h of reperfusion with continuous left ventricular function monitoring. At the end, the hearts were subjected to either measurement of infarct size or cardiomyocyte apoptosis. Some hearts (from different sets of experiments) were used for transmission electron microscopy (TEM), confocal microscopy, or Western blot analysis. Tunicamycin and thapsigargin, irrespective of the dose, induced sufficient ER stress, as evidenced by the increased phosphorylation or activation of eIF2α and PERK. Such ER stress potentiated autophagy in the heart, as evidenced by an increase in LC3-II, beclin-1, and Atg5. This was also supported by TEM, clearly showing the production of autophagosomes, and by confocal microscopy, showing upregulation of eIF2α and beclin-1. The autophagy produced with lower doses of tunicamycin and thapsigargin in the face of myocardial I/R resulted in reduction of the I/R injury, as evidenced by improved left ventricular function and reduced myocardial infarct size and cardiomyocyte apoptosis. In concert, an induction of GRP78 and activation of Akt and Bcl-2 occurred. The higher doses conversely were detrimental for the heart and were associated with induction of CHOP and downregulation of Akt. The results thus display the proof of concept that induction of autophagy by ER stress (therapeutic amount) before ischemia (similar to ischemic preconditioning) could reduce subsequent lethal ischemic reperfusion injury.
Antioxidants & Redox Signaling 06/2011; 14(11):2191-200. · 8.20 Impact Factor
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ABSTRACT: In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.
Phytotherapy Research 01/2011; 25(1):128-36. · 2.09 Impact Factor
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Balazs Varga,
Krisztina Szabadfi,
Peter Kiss,
Eszter Fabian,
Andrea Tamas,
Monika Griecs,
Robert Gabriel,
Dora Reglodi,
Adam Kemeny-Beke,
Zsuzsanna Pamer,
Zsolt Biro,
Arpad Tosaki,
Tamas Atlasz, Bela Juhasz
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This has been proven in different models of retinal degeneration. The in vivo protective effects of PACAP have been shown in retinal degeneration induced by kainic acid, optic nerve transection and ischemia. We have previously shown by morphological, morphometrical and immunohistochemical analyses that intravitreal PACAP administration protects against monosodium glutamate (MSG)-induced damage in neonatal rats. The question was raised whether these apparent morphological improvements by PACAP administration also lead to functional amelioration in MSG-induced retinal damage. The aim of the present study was to investigate the functional consequences of MSG treatment and the subsequent PACAP administration using electroretinographic measurements. The histological and morphometrical analyses supported the earlier findings that PACAP protected the retina in MSG-induced excitotoxicity. ERG recordings revealed a marked decrease in both the b- and a-wave values, reflecting the function of the inner retinal layers and the photoreceptors, respectively. In retinas receiving intravitreal PACAP treatment, these values were significantly increased. Thus, the functional outcome, although not parallel with the morphology, was significantly improved after PACAP treatment. The present observations are important from the clinical point of view showing, for the first time, that PACAP treatment is able to improve the functional properties of the retina in excitotoxic damage.
Journal of Molecular Neuroscience 01/2011; 43(1):44-50. · 2.50 Impact Factor
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Heibatullah Kalantari,
Mohammadtaha Jalali,
Amir Jalali,
Abobakr Salimi,
Foad Alhalvachi,
Balazs Varga, Bela Juhasz,
Anita Jakab,
Adam Kemeny-Beke,
Rudolf Gesztelyi,
Arpad Tosaki,
Judit Zsuga
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ABSTRACT: The efficacy of a crude hydro-alcoholic extract of Cassia fistula (golden shower tree) fruit to protect the kidney against bromobenzene-induced toxicity was studied. Negative control mice received normal saline; positive control mice were given 460 mg/kg of bromobenzene; Cassia fistula treated mice received 200, 400, 600 and 800 mg/kg of Cassia fistula fruit extract followed by 460 mg/kg bromobenzene (daily by oral gavage for 10 days). On the 11th day, the mice were sacrificed, blood samples were obtained to assess blood urea nitrogen (BUN) and creatinine levels, and kidneys were removed for histological examination. We found that bromobenzene induced significant nephrotoxicity reflected by an increase in levels of BUN and creatinine that was dose dependently prevented by the Cassia fistula fruit extract. The nephroprotective effect of the Cassia fistula fruit extract was confirmed by the histological examination of the kidneys. To the best of our knowledge, this is the first study to demonstrate the protective effect of Cassia fistula in nephrotoxicity.
Human & Experimental Toxicology 01/2011; 30(10):1710-5. · 1.31 Impact Factor
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ABSTRACT: Several recent studies have shown the protective effects of resveratrol in various experimental conditions and pathological animal models. Clinical studies also indicate the beneficial effects of resveratrol in different human diseases. Resveratrol produces a cascade against of events from the initial death-provoking signal, DNA fragmentation, and cell death. Researchers recognized the beneficial effect of resveratrol, as an important component, of the overall injury that occurs in various disorders such as oxidative stress, myocardial injury, anticancer activity, antidiabetic activity, and antihypercholesterolemic effects. Many mechanisms have been proposed for the initiation of protective effects of resveratrol in various pathological events, and considerable evidence exists to indicate that many mediators are involved in the resveratrol-induced protection. The present review focuses on the history, and the beneficial effects and mechanisms of resveratrol in oxidative stress, myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic activities, and discusses those therapeutic tools, which warrant becoming clinically important.
Current pharmaceutical biotechnology 12/2010; 11(8):810-8. · 3.40 Impact Factor
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ABSTRACT: The present study examined the efficacy of using longevinex, a commercially available resveratrol formulation, to lower blood cholesterol in hypercholesteromic rabbits. New Zealand white rabbits were randomly divided into two groups (n = 6 per group), one group was given high cholesterol diet for 3 months while the other group fed regular diet served as control. The high cholesterol diet fed group was further subdivided into two groups (n = 6 per group), one group was given longevinex resveratrol while the other group given vehicle only served as control. Longevinex was given by gavaging up to a period of 6 months. Longevinex-treated rabbits exhibited lowering of plasma cholesterol level. Inhibition of arterial plaque formation was noticed even after 1 month. Longevinex-treated hearts demonstrated improved ventricular recovery when isolated working hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion. Aortic flow and developed pressure during post-ischemic reperfusion period were significantly higher for the longevinex-treated hearts compared to those in control group of hearts. Myocardial infarct size was also lower in the treated group compared to that for the untreated group. These results indicate cholesterol-lowering ability of longevinex, which appears to reflect in its ability to protect the hypercholesteromic hearts from ischemic reperfusion injury.
Molecular and Cellular Biochemistry 11/2010; 348(1-2):199-203. · 2.06 Impact Factor
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ABSTRACT: The receptorial responsiveness method (RRM) was proposed to characterize changes in the concentration of degradable agonists in the microenvironment of their receptors. The characterization is done by providing concentrations of a stable agonist for the same receptor that is equieffective with the change in concentration to be characterized. RRM is based on the analysis of concentration-effect (E/c) curves reflecting the simultaneous action of the degradable and the stable agonist. In the present study, we investigated whether dissimilar affinity and (or) efficacy of the coacting agonists as well as the steepness of the E/c curves influence the reliability of RRM. E/c curves were simulated based on the operational model and then analyzed with RRM. We found that dissimilarity in affinity of the coacting agonists did not affect the accuracy of RRM estimates. In contrast, accuracy of the estimation depended on the magnitude of the concentration to be assessed, the operational slope factor, and the operational efficacy ratio of the coacting agonists. However, our results suggest that proper choice of a stable agonist for a degradable one can help to ensure reliable results, since information about the change in concentration of a degradable agonist is otherwise difficult to obtain.
Canadian Journal of Physiology and Pharmacology 11/2010; 88(11):1061-73. · 1.95 Impact Factor
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ABSTRACT: The receptorial responsiveness method (RRM) was proposed to estimate changes in the concentration of an agonist in the microenvironment of its receptor. Usually, this is done by providing the equieffective concentration of another agonist for the same receptor or for a largely overlapping postreceptorial signaling ("test agonist"). The RRM is a special nonlinear regression algorithm to analyze a concentration-response (E/c) curve that represents the simultaneous actions of a single agonist concentration to be estimated and of increasing concentrations of the test agonist. The aim of this study was to explore whether asymmetry of the E/c curve to be analyzed influences the reliability of the RRM. For this purpose, computer simulation was performed by constructing symmetric and asymmetric E/c curves using the operational model of agonism, and then these curves were analyzed with the RRM. To perform the RRM, 2 types of equations were used: one involving the Hill equation, the simplest model of the E/c relationship, and one containing the Richards equation, an advanced model properly handling E/c curve asymmetry. Results of this study indicate that E/c curve asymmetry does not significantly influence the accuracy of the estimates provided by the RRM. Thus, when using the RRM, it is not necessary to replace the Hill equation with the Richards equation to obtain useful estimates. Furthermore, it was found that estimation of a high concentration of a high-efficacy agonist can fail when the RRM is performed with a low-efficacy test agonist in a system characterized by a small operational slope factor.
Canadian Journal of Physiology and Pharmacology 11/2010; 88(11):1074-83. · 1.95 Impact Factor
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ABSTRACT: In the present study, hepatoprotective effect of Cassia fistula fruit extract was investigated in mice. Animals were divided into six groups receiving normal saline (1), bromobenzene (460 mg/kg) alone (2) and together with increasing doses (200, 400, 600, 800 mg/kg) of a crude hydro-alcoholic extract of Cassia fistula fruit (3-6, respectively). All administrations were carried out orally, daily, for 10 days. On the 11th day, animals were sacrificed. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT) were determined; serum levels of direct and total bilirubin were measured; furthermore, livers were prepared for histological examination. Our results showed that bromobenzene treatment alone elicited a significant increase in activities of AST, ALT, ALP (but not γGT), and it significantly elevated the levels of direct and total bilirubin. Co-treatment with Cassia fistula fruit extract, however, significantly and dose-dependently decreased the above-mentioned enzyme activities (with exception of γGT) and bilirubin levels, producing a recovery to the naive state. The protective effect of Cassia fistula fruit extract against liver injury evoked by bromobenzene was confirmed by histological examination as well. In conclusion, the Cassia fistula fruit extract has significant hepatoprotective effect in our murine model.
Human & Experimental Toxicology 10/2010; 30(8):1039-44. · 1.31 Impact Factor
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ABSTRACT: ABSTRACT Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (hsp-32) is a stress induced cytoprotective protein. The present investigation evaluated the capacity of HO-1 to reduce the incidence of reperfusion-induced ventricular fibrillation (VF) and infarct size. HO-1 transgenic (Tg) mice were generated using a rat HO-1 genomic transgene. Isolated mouse hearts obtained from Tg and nontransgenic (NTg) groups were exposed to 20 min of global ischemia and 120 min of reperfusion. Epicardial ECG was recorded to monitor the incidence of reperfusion-induced VF and at the end of the reperfusion period, detection of HO-1 by immunohistochemistry and measurement of infarct size using the TTC method were carried out. Results shown here provide additional support for cardioprotective effects of HO-1 as evidenced by the reduced infarct size. Moreover, overexpression of the HO-1 efficiently reduced the incidence of ischemia/reperfusion (I/R)-induced VF in HO-1 Tg mice.
Journal of Cellular and Molecular Medicine 08/2010; · 4.13 Impact Factor
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ABSTRACT: A plant-based diet reduces the risk for the development of several chronic diseases, such as ischemic heart disease or cancer due to natural compounds found in plants. Numerous cereals, berries, fruits, and vegetables, including sour cherry (Prunus cerasus), which is a favored fruit worldwide, contain biological active components. The antioxidant components of the sour cherry seed kernel have not been investigated until now. The aim of our study was to isolate and analyze the bioactive constituents of sour cherry seed kernel. We separated the oil fraction of the kernel; then the remaining solid fraction was dried, and the oil-free kernel extract was further analyzed. Our results show that sour cherry seed kernel oil contains vegetable oils including unsaturated fatty acids, oleic acids, alpha-tocopherol, tocotrienols, and tocopherol-like components. The components of the solid fraction include various bioactive structures such as polyphenols, flavonoids, vegetable acids, and pro- and anthocyanidins, which could have useful therapeutic effects in the prevention of various vascular diseases.
Journal of medicinal food 08/2010; 13(4):905-10. · 1.39 Impact Factor
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ABSTRACT: Resveratrol, a grape- and red wine-derived polyphenolic phytoalexin, shows diverse health benefits including cardioprotection. Recent studies implicate that resveratrol displays hormetic action, protecting the cells at a lower dose while killing them at relatively higher doses. Because such hormetic behaviour may have a significant impact on epidemiological and clinical studies, the present study sought to determine dose-response curves for resveratrol action. In parallel, another resveratrol formulation was tested, namely, Longevinex (Resveratrol Partners LLC, USA). A group of rats were force-fed three different doses of resveratrol or Longevinex (2.5 mg/kg, 25 mg/kg and 100 mg/kg) for up to 30 days, while the control group was only given placebo. The results showed hormesis for pure resveratrol, which was cardioprotective at lower doses and detrimental for higher doses, but surprisingly Longevinex did not display any hormetic action. In the concentration range studied, Longevinex remained cardioprotective even at 100 mg/100 g body weight - a dose that killed 100% of the hearts when tested with pure resveratrol. To further test whether Longevinex doses are beneficial for other animal species, Longevinex was gavaged to a group of rabbits for six months, and showed exactly the same degree of cardioprotection. Cardioprotection was examined in isolated working hearts subjected to 30 min of ischemia followed by 2 h of reperfusion; left ventricular performance and infarct size was also examined. It appears that Longevinex does not show any hormetic action, while resveratrol clearly does.
Experimental and clinical cardiology 01/2010; 15(4):e134-8. · 0.58 Impact Factor
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Istvan Lekli,
Diptarka Ray,
Subhendu Mukherjee,
Narasimman Gurusamy,
Md Kaimul Ahsan, Bela Juhasz,
Istvan Bak,
Arpad Tosaki,
Mihaela Gherghiceanu,
Lawrence M Popescu,
Dipak K Das
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ABSTRACT: This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.
Journal of Cellular and Molecular Medicine 10/2009; 14(10):2506-18. · 4.13 Impact Factor
