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Cardioprotective Effects (cardioprotective + effects)
Selected AbstractsCardioprotective Effects of Nigella sativa Oil on Cyclosporine A-Induced Cardiotoxicity in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Uz Ebru However, it has been demonstrated that this drug produces side-effects in several organs, particularly in the kidney and in the heart. Nigella sativa oil has long been used in folk medicine for a wide range of illnesses. One of the potential properties of N. sativa oil is the ability of one or more of its constituents to reduce toxicity due to its antioxidant activities. The antioxidant effects of N. sativa oil have been examined using different hepatic and kidney toxicity in in vivo murine models. The aim of this study was to evaluate the effects of N. sativa oil in the antioxidant enzyme status and myocardium of cyclosporine-A-treated rats. This study included 24 male Wistar albino young healthy rats (8,12 weeks) weighing 150,200 g. The control group received sunflower oil (21 days, 2 ml/kg/day, orally) without any treatment. The second group received only N. sativa oil (21 days, 2 ml/kg, orally) (N. sativa oil group). The animals in the third group received only cyclosporine A (21 days, 25 mg/kg, orally) (cyclosporine A group). The animals in the fourth group were treated with cyclosporine A (21 days, 25 mg/kg, orally) and starting one day before cyclosporine A administration were treated with N. sativa oil (21 days, 2 ml/kg, orally) (cyclosporine A +N. sativa oil group). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the heart tissues were significantly reduced in the cyclosporine A group compared to control values. Nigella sativa oil treatment caused an increase in the activities of SOD, CAT and GSH-Px compared to the control group. Malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were increased in the cyclosporine A-treated group in comparison with the control and N. sativa groups. Co-administration of N. sativa oil and cyclosporine A abrogated the cyclosporine A-induced MDA, N. sativa oil and PC increase compared to the cyclosporine A group. The results of our study show that pre-treatment with N. sativa oil reduced the subsequent cyclosporine A injury in rat heart, demonstrated by normalized cardiac histopathology, decrease in lipid peroxidation, improvement in antioxidant enzyme status and cellular protein oxidation. [source] Cardioprotective Effects of Angiotensin II Type 1 Receptor Blockade with Olmesartan on Reperfusion Injury in a Rat Myocardial Ischemia-Reperfusion ModelCARDIOVASCULAR THERAPEUTICS, Issue 1 2010Wangde Dai We determined the effects of olmesartan on infarct size and cardiac function in a rat ischemia/reperfusion model. Rats underwent 30 min of left coronary artery (CA) occlusion followed by 2 h of reperfusion. In protocol 1, the rats received (by i.v.) 1 mL of vehicle at 10 min after CA occlusion (Group 1, n = 15); olmesartan (0.3 mg/kg) at 10 min after CA occlusion (Group 2, n = 15); 1 mL of vehicle at 5 min before CA reperfusion (Group 3, n = 15); or olmesartan (0.3 mg/kg) 5 min before CA reperfusion (Group 4, n = 15). In protocol 2, the rats received (by i.v.) 1 mL of vehicle at 5 min before CA reperfusion (Group 5, n = 21); or olmesartan (3 mg/kg) at 5 min before CA reperfusion (Group 6, n = 21). Systemic hemodynamics, left ventricular (LV) function, LV ischemic risk zone, no-reflow zone, and infarct size were determined. In protocol 1, olmesartan (0.3 mg/kg) did not affect blood pressure (BP), heart rate, LV ± dp/dt or LV fractional shortening during the experimental procedure, and did not alter no-reflow or infarct size. In protocol 2, olmesartan (3 mg/kg) significantly reduced infarct size to 21.7 ± 4.1% from 34.3 ± 4.1% of risk zone in the vehicle group (P= 0.035), but did not alter the no-reflow size. Prior to CA reperfusion, olmesartan (3 mg/kg) significantly reduced mean BP by 22% and LV ±dp/dt, but did not affect heart rate. At 2 h after reperfusion, olmesartan significantly decreased heart rate by 21%, mean BP by 14%, and significantly increased LV fractional shortening from 54.1 ± 1.4% to 61.3 ± 1.6% (P= 0.0018). Olmesartan significantly reduced myocardial infarct size and improved LV contractility at a dose (3 mg/kg) with systemic vasodilating effects but not at a lower dose (0.3 mg/kg) without hemodynamic effects. [source] DY-9760e, a Novel Calmodulin Inhibitor, Exhibits Cardioprotective Effects in the Ischemic HeartCARDIOVASCULAR THERAPEUTICS, Issue 2 2006Kohji Fukunaga ABSTRACT DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H -indazole dihydrochloride-3.5 hydrate) inhibits Ca2+/CaM-dependent nitric oxide synthase (NOS), thereby inhibiting nitric oxide (NO) production. In cardiomyocytes from ischemic rat heart NO and superoxide levels are increased causing protein tyrosine nitration. In hearts subjected to ischemia/reperfusion DY-9760e totally abolishes protein tyrosine nitration. Notably, DY-9760e also inhibits calpain and cas-pase-3 activation that occurs prior to apoptosis in cardiomyocytes. In ischemic hearts fodrin is the substrate for calpain. DY-9760e inhibits fodrin breakdown in the peri-infarct area rather than in the infarct core. In the ischemic rat brain DY-9760e inhibits caspase-3-induced proteolysis of calpastatin, an endogenous calpain inhibitor, suggesting that crosstalk between calpain and caspase-3 is mediated by calpastatin breakdown. Thus, DY-9760e rescues neurons and cardiomyocytes from ischemic injury by inhibiting crosstalk between calpain and caspase-3 as well as protein tyrosine nitration. [source] Effects of sulfonylureas on mitochondrial ATP-sensitive K+ channels in cardiac myocytes: implications for sulfonylurea controversyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2006Toshiaki Sato Abstract Background Mitochondrial ATP-sensitive K+ (mitoKATP) channel plays a key role in cardioprotection. Hence, a sulfonylurea that does not block mitoKATP channels would be desirable to avoid damage to the heart. Accordingly, we examined the effects of sulfonylureas on the mitoKATP channel and mitochondrial Ca2+ overload. Methods Flavoprotein fluorescence in rabbit ventricular myocytes was measured to assay mitoKATP channel activity. The mitochondrial Ca2+ concentration was measured by loading cells with rhod-2. Results The mitoKATP channel opener diazoxide (100 µM) reversibly increased flavoprotein oxidation to 31.8 ± 4.3% (n = 5) of the maximum value induced by 2,4-dinitrophenol. Glimepiride (10 µM) alone did not oxidize the flavoprotein, and the oxidative effect of diazoxide was unaffected by glimepiride (35.4 ± 3.2%, n = 5). Similarly, the diazoxide-induced flavoprotein oxidation was unaffected both by gliclazide (10 µM) and by tolbutamide (100 µM). Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca2+ overload, and the intensity of rhod-2 fluorescence increased to 197.4 ± 7.2% of baseline (n = 11). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca2+ overload (149.6 ± 5.1%, n = 11, p < 0.05 versus ouabain alone), and the effect was antagonized by the mitoKATP channel blocker 5-hydroxydecanoate (189.8 ± 27.8%, n = 5) and glibenclamide (193.1 ± 7.7%, n = 8). On the contrary, cardioprotective effect of diazoxide was not abolished by glimepiride (141.8 ± 7.8%, n = 6), gliclazide (139.0 ± 9.4%, n = 5), and tolbutamide (141.1 ± 4.5%, n = 7). Conclusions Our results indicate that glimepiride, gliclazide, and tolbutamide have no effect on mitoKATP channel, and do not abolish the cardioprotective effects of diazoxide. Therefore, these sulfonylureas, unlike glibenclamide, do not interfere with the cellular pathways that confer cardioprotection. Copyright © 2006 John Wiley & Sons, Ltd. [source] Thaliporphine protects ischemic and ischemic-reperfused rat hearts via an NO-dependent mechanismDRUG DEVELOPMENT RESEARCH, Issue 3 2001Li-Man Hung Abstract In ischemia or ischemia-reperfusion (I/R), nitric oxide (NO) can potentially exert several beneficial effects. Thaliporphine, a natural alkaloid with Ca2+ channel-activating and Na+/K+ channel-blocking activities, increased NO levels and exerted cardioprotective action in ischemic or I/R rats. The role of NO in the cardioprotective actions of thaliporphine was assessed. The severity of rhythm disturbances and mortality in anesthetized rats with either coronary artery occlusion for 30 min, or 5 min followed by 30-min reperfusion, were monitored and compared in thaliporphine- vs. placebo-treated groups. Thaliporphine treatment significantly increased NO and decreased lactate dehydrogenase (LDH) levels in the blood during the end period of ischemia or I/R. These changes in NO and LDH levels by thaliporphine were associated with a reduction in the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischemic or I/R period. The mortality of animals was also completely prevented by 1 × 10,8 moles/kg of thaliporphine. In animals subjected to 4 h of left coronary artery occlusion, 1 × 10,7 moles/kg of thaliporphine dramatic reduced cardiac infarct zone from 46 ± 6% to 7.1 ± 1.9%. Inhibition of NO synthesis with 3.7 × 10,6 moles/kg of N, -nitro-L-arginine methyl ester (L-NAME) abolished the beneficial effects of thaliporphine during 30 min or 4 h myocardial ischemia. However, the antiarrhythmic activity and mortality reduction efficacy of thaliporphine during reperfusion after 5 min of ischemia was only partially antagonized by L-NAME. These results showed that thaliporphine efficiently exerted the cardioprotections either in acute or prolonged coronary artery occlusion or occlusion-reperfusion situations. The fact that thaliporphine induced cardioprotective effects were abrogated by L-NAME indicates that NO is an important mediator for the cardioprotective effects of thaliporphine in acute or prolonged ischemia, whereas antioxidant activities may contribute to the protection of I/R injury. Drug Dev. Res. 52:446,453, 2001. © 2001 Wiley-Liss, Inc. [source] A diet enriched with mackerel (Scomber scombrus),derived products improves the endothelial function in a senior population (Prevención de las Enfermedades Cardiovasculares: Estudio Santoña , PECES project)EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2009J. R. De Berrazueta ABSTRACT Background, Regular consumption of fish reduces cardiovascular risks. Here, we investigate if the consumption of products with mackerel (Scomber scombrus) with 8·82 g of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content per 100 g of product improves parameters of endothelial function in a controlled population. Materials and methods, Subjects maintained a 12-week diet with products with mackerel. The population consisted of 58 senior subjects (12 withdrawals, 25 women), aged 82·08 ± 8·13 years (Group A). Twenty-three senior subjects (13 women) on a regular diet were used as the control group (Group B). Subjects of Group A received 57 portions throughout 12 weeks (four to five portions a week of products with a mean EPA + DHA content of 2·5 g a day). A continuous follow-up and a final evaluation were performed to determine the level of consumption. Plasma samples were stored at ,70 °C for a biochemical study. Endothelial function was analysed by reactive hyperemia with a mercury strain gauge plethysmography with measurement of blood flow in the forearm, both baseline and at the end of the 12-week diet. Results, Endothelium-dependent vasodilatation significantly increased in Group A subjects (P < 0·001). No changes were found in Group B. The subgroup analyses showed that improvements were produced in Group A subjects without cardiovascular disease (P < 0·001). Nitrites/nitrates and von Willebrand factor plasma concentrations were higher in participants after the 12-week diet. Conclusions, The consumption of mackerel meat products improves endothelium-dependent, flow-mediated vasodilatation in a senior population. This finding might explain some of the cardioprotective effects of fish consumption. [source] Dietary intake of differently fed salmon: a preliminary study on contaminantsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2006C. Bethune Abstract Background, In a previous study, a group of coronary heart disease (CHD) patients exhibited positive cardioprotective effects of fatty acids derived from a diet of farmed Atlantic salmon fed fish oil (Seierstad et al. 2005). This follow-up study examines these patients for plasma exposure to selected organic and inorganic contaminants found in seafood that may detract from the benefits of eating oily fish. Methods, The study design was from Seierstad et al. (2005), where 58 patients were allocated into three groups consuming 700 g week,1 of differently fed Atlantic salmon (Salmo salar) fillets for 6 weeks: 100% fish oil (FO), 100% rapeseed oil (RO), or 50% of each (FO/RO). Results, Different fillets showed graded levels (FO > FO/RO > RO) of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DLPCBs), indicator PCBs, polybrominated diphenyl ethers (PBDEs), and arsenic (As). Mercury (Hg) and lead (Pb) levels were similar across the three types of fillets. After 6 weeks of consumption, patient levels of PCDDs, DLPCBs, and PCBs in plasma decreased as the dietary intake of these contaminants increased. Plasma PBDEs only showed increases for the FO patients. Levels of inorganic contaminants in plasma showed only slight changes over the study period. Conclusions, These results show a reduction in the use of marine oils in fish feed reduces organic contaminant levels in farmed salmon while still providing a good dietary source of marine fatty acids. [source] High-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarctionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005L. Zhang Abstract Background, Several clinical trials have suggested that a metabolic cocktail of glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute myocardial infarction (AMI). It has also been reported that Fas-mediated apoptosis plays an important role in ischaemic/reperfusion injury in the rat model. This study was designed to evaluate the interaction of ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration in patients with AMI. Materials and methods, Seventy-four patients presenting with AMI who underwent reperfusion therapy were randomized into a GIK group (n = 35) receiving high-dose GIK for 24 h or a vehicle group (n = 39). Thirty-four control subjects were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the soluble sFas and sFasL plasma concentration at baseline, 24 h (h), 3 day (d), 7 d and 14 d. Results, Soluble Fas and sFas-L serum concentrations ([sFas] and [sFas-L]) of patients with AMI were significantly elevated at baseline as compared with normal controls (NCs; P < 0·01 vs. NC). The sFas in the GIK and vehicle groups markedly decreased 24 h after the GIK infusion (10·7,5·9 ng mL,1 and 9·7,6·5 ng mL,1; P < 0·01 vs. baseline) and then increased during the 3,7-d period (5·9,12·1 ng mL,1 and 6·5,11·1 ng mL,1; P < 0·01 vs. 24 h). The GIK group demonstrated reduced sFas (12·1,5·9 ng mL,1) at 14 d (P < 0·01 vs. 7 d), with no concomitant changes in the vehicle group. The sFas-L in the GIK and vehicle groups was not significant different during the 14-d period. Conclusions, These results indicate that the sFas and sFasL in patients with AMI increased significantly compared with NC. Owing to the cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely re-establishment of nutritive perfusion should be strongly considered as a treatment of choice for AMI. Additionally, sFas may be a valuable marker of the physiological response to ischaemic/reperfusion injury and reperfusion associated with high-dose GIK treatment. [source] Alcohol and mortality: methodological and analytical issues in aggregate analysesADDICTION, Issue 1s1 2001Thor Norström This supplement includes a collection of papers that aim at estimating the relationship between per capita alcohol consumption and various forms of mortality, including mortality from liver cirrhosis, accidents, suicide, homicide, ischaemic heart disease, and total mortality. The papers apply a uniform methodological protocol, and they are all based on time series data covering the post-war period in the present EU countries and Norway. In this paper we discuss various methodological and analytical issues that are common to these papers. We argue that analysis of time series data is the most feasible approach for assessing the aggregate health consequences of changes in population drinking. We further discuss how aggregate data may also be useful for judging the plausibility of individual-level relationships, particularly those prone to be confounded by selection effects. The aggregation of linear and curvilinear risk curves is treated as well as various methods for dealing with the time-lag problem. With regard to estimation techniques we find country specific analyses preferable to pooled cross-sectional/time series models since the latter incorporate the dubious element of geographical co-variation, and conceal potentially interesting variations in alcohol effects. The approach taken in the papers at hand is instead to pool the country specific results into three groups of countries that represent different drinking cultures; traditional wine countries of southern Europe, beer countries of central Europe and the British Isles and spirits countries of northern Europe. The findings of the papers reinforce the central tenet of the public health perspective that overall consumption is an important determinant of alcohol-related harm rates. However, there is a variation across country groups in alcohol effects, particularly those on violent deaths, that indicates the potential importance of drinking patterns. There is no support for the notion that increases in per capita consumption have any cardioprotective effects at the population level. [source] Tocotrienols and cancer: Beyond antioxidant activityEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 4 2007Kalanithi Nesaretnam Abstract The edible oil industry has emerged as an important provider of raw material for the extraction of vitamin,E. Vegetable oils, especially the seed oils, are rich sources of tocopherols. However, in palm oil, vitamin,E occurs as a complex mixture of tocopherols and tocotrienols. Various tocotrienol isomers of vitamin,E in palm oil have been reported to possess interesting biological and physiological properties not generally evident with tocopherol-rich vitamin,E preparations. They include potential blood cholesterol-lowering and cardioprotective effects, more efficient antioxidant activity in biological systems, and possible anti-cancer and neuroprotective effects. With the emergence of palm oil as the largest edible oil in world markets, technology is now available to extract tocotrienol-rich palm vitamin,E. Initiatives in Malaysia to manufacture biodiesel will further generate large amounts of micronutrients, especially tocotrienols, to be available to the nutraceutical and functional food industry. [source] Sarcolemmal and mitochondrial KATP channels and myocardial ischemic preconditioningJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2002J. N. Peart Abstract Ischemic preconditioning (IPC) is the phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of arrhythmias. While many substances and pathways have been proposed to play a role in the signal transduction mediating the cardioprotective effect of IPC, overwhelming evidence indicates an intimate involvement of the ATP-sensitive potassium channel (KATP channel) in this process. Initial hypotheses suggested that the surface or sarcolemmal KATP (sarcKATP) channel mediated the cardioprotective effects of IPC. However, much research has subsequently supported a major role for the mitochondrial KATP channel (mitoKATP) as the one involved in IPC-mediated cardioprotection. This review presents evidence to support a role for the sarcKATP or the mitoKATP channel as either triggers and/or downstream mediators in the phenomenon of IPC. [source] Inhibition of apoptosis by progesterone in cardiomyocytesAGING CELL, Issue 5 2010Stephen Morrissy Summary While gender-based differences in heart disease have raised the possibility that estrogen (ES) or progesterone (PG) may have cardioprotective effects, recent controversy regarding hormone replacement therapy has questioned the cardiac effects of these steroids. Using cardiomyocytes, we tested whether ES or PG has protective effects at the cellular level. We found that PG but not ES protects cardiomyocytes from apoptotic cell death induced by doxorubicin (Dox). PG inhibited apoptosis in a dose-dependent manner, by 12 ± 4.0% at 1 ,m and 60 ± 1.0% at 10 ,m. The anti-apoptotic effect of PG was also time dependent, causing 18 ± 5% or 62 + 2% decrease in caspase-3 activity within 1 h or 72 h of pretreatment. While PG causes nuclear translocation of its receptor within 20 min, the cytoprotective effect of PG was canceled by mifepristone (MF), a PG receptor antagonist. Analyses using Affymetrix high-density oligonucleotide array and RT-PCR found that PG induced Bcl-xL, metallothionine, NADPH quinone oxidoreductase 1, glutathione peroxidase-3, and four isoforms of glutathione S-transferase. Western blot analyses revealed that PG indeed induced an elevation of Bcl-xL protein in a dose- and time-dependent manner. Nuclear run-on assay indicated that PG induced Bcl-xL gene transcription. Inhibiting the expression of Bcl-xL using siRNA reduced the cytoprotective effect of PG. Our data suggests that PG induces a cytoprotective effect in cardiomyocytes in association with induction of Bcl-xL gene. [source] Bacopa monniera protects rat heart against ischaemia,reperfusion injury: role of key apoptotic regulatory proteins and enzymesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2010Ipseeta Ray Mohanty Abstract Objectives, Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia,reperfusion (I-R) injury. Methods, Forty-eight rats were randomly divided into four groups (12 in each group): sham group (no ischaemia,reperfusion injury), B. monniera control group (orally fed B. monniera at a dose of 75 mg/kg, for three weeks); ischaemia,reperfusion control group(subjected to ischaemia,reperfusion-induced myocardial injury) and B. monniera -treated group (same protocol as ischaemia,reperfusion control group except that rats also fed B. monniera). Key findings, Post-ischaemic reperfusion injury resulted in significant cardiac necrosis, apoptosis, depression of heart rate, decline in antioxidant status and elevation in lipid peroxidation. Oral administration of B. monniera per se for three weeks to healthy rats caused augmentation of myocardial antioxidants, superoxide dismutase, catalase and glutathione, along with induction of heat shock protein 72 (HSP72). Ischaemia,reperfusion-induced biochemical and histopathological perturbations were significantly prevented by B. monniera (75 mg/kg) pre-treatment. Interestingly, B. monniera also restored the antioxidant network of the myocardium and reduced myocardial apoptosis, caspase 3 and Bax protein expression. Conclusions, Histopathological studies and myocardial creatine phosphokinase content further confirmed the cardioprotective effects of B. monniera (75 mg/kg) in the experimental model of ischaemia,reperfusion injury. The study provides scientific basis for the putative therapeutic effect of B. monniera in ischaemic heart disease. [source] The Effects of Nuts on Coronary Heart Disease RiskNUTRITION REVIEWS, Issue 4 2001Penny M. Kris-Etherton Ph.D. Epidemiologic studies have consistently demonstrated beneficial effects of nut consumption on coronary heart disease (CHD) morbidity and mortality in different population groups. Clinical studies have reported total and low-density lipoprotein cholesterol-lowering effects of heart-healthy diets that contain various nuts or legume peanuts. It is evident that the favorable fatty acid profile of nuts (high in unsaturated fatty acids and low in saturated fatty acids) contributes to cholesterol lowering and, hence, CHD risk reduction. Dietary fiber and other bioactive constituents in nuts may confer additional cardioprotective effects. [source] Protective effects of steroids from Allium chinense against H2O2 -induced oxidative stress in rat cardiac H9C2 cellsPHYTOTHERAPY RESEARCH, Issue 3 2010Gang Ren Abstract Allium chinense, a traditional herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years. In this study, A. chinense steroids (ACSs) including three steroidal glycosides and their parent aglycones were isolated from the bulbs of A. chinense. For the first time, their cardioprotective effects were evaluated in cultured rat cardiac H9C2 cells by pretreatment with ACSs for 24,h before exposure to 0.2,mm H2O2. The results showed the cell viability decreased markedly when H9C2 cells were incubated with 0.2,mm H2O2 alone for 2,h, while the cell lipid peroxidation (estimated by the excessive production of nitric oxide and malondialdehyde) and intracellular free calcium concentration ([Ca2+]i) increased significantly. The addition of 20,,m (below the toxic concentration) of ACSs notably attenuated the cellular injury induced by H2O2. The effects of ACSs in our experiments were similar to those of nimodipine, a clinically applied calcium channel blocker. Preliminary analysis of the structure,activity relationship indicated that ACSs with a spirostane-type skeleton exhibited stronger protection than that with a furostane-type skeleton, and glycosylation of the steroids could substantially lower the protective activities. The above results suggested the protective effects of steroids originated from A. chinense on the oxidative injury of H9C2 cells and ACSs may have potential for preventing cardiac injuries induced by oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cardioprotective effect of sasanquasaponin preconditioning via bradykinin-NO pathway in isolated rat heartPHYTOTHERAPY RESEARCH, Issue 8 2009Zhangping Liao Abstract Sasanquasaponin (SQS) is an effective component of Camellia oleifera Abel. This study was designed to investigate the cardioprotective effect of SQS against ischemia-reperfusion (I/R) injury and the possible mechanism in isolated rat hearts. These hearts were pretreated by SQS only or SQS and HOE140 in different groups, and then subjected to I/R injury. Hemodynamic parameters, oxidative injury, and NO level were measured. The results showed that SQS preconditioning could decrease the incidences of arrhythmias and improve the heart functions. In addition, SQS preconditioning could protect isolated I/R injured heart against lipid peroxidation, as evidenced by increases in SOD and GSH-Px activity, and by decreases in contents of MDA, ROS generation. However, HOE140 treatment reversed all these indexes. NO production was significantly decreased after a treatment with HOE140. So we can propose that SQS preconditioning could induce the cardioprotective effects and the possible mechanism was that the activation of bradykinin-NO system by SQS preconditioning had an inhibition effect on ROS generation in isolated heart. Copyright © 2009 John Wiley & Sons, Ltd. [source] Mast cells, peptides and cardioprotection , an unlikely marriage?AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2009S. K. Walsh Summary 1,Mast cells have classically been regarded as the ,bad guys' in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic. 2,Many peptides, such as ET-1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide-induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection. 3,The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system. [source] Metformin Induces Cardioprotection against Ischaemia/Reperfusion Injury in the Rat Heart 24 Hours after AdministrationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2008Lasse Solskov The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 ± 3.9%versus 36.7 ± 3.6%, P < 0.01, n = 8,14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-,2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin. [source] Delayed Protection of Tetramethylpyrazine on Neonatal Rat Cardiomyocytes Subjected to Anoxia-Reoxygenation InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007He-Ping Chen Cultured neonatal rat cardiomyocytes were preconditioned using TMP at different concentrations (100, 200 and 500 µM). Cell viability, lactate dehydrogenase release, malondialdehyde formation, superoxide dismutase activity and glutathione peroxidase activity were measured to determine the protective effects against anoxia-reoxygenation injury. The expression of heat shock protein 70 (Hsp70) was measured 24 hr after TMP preconditioning by Western blot analysis. The results showed that TMP decreased lactate dehydrogenase release, increased cell viability, suppressed malondialdehyde formation and augmented activities of superoxide dismutase and glutathione peroxidase in a concentration-dependent manner. Moreover, the delayed protection was abolished by pre-treating with either protein kinase C inhibitor chelerythrine chloride or PD98059, a selective inhibitor of extracellular signal-regulated protein kinase 1/2, respectively, and the expression of Hsp70 was significantly increased in 24 hr after TMP preconditioning that was also suppressed by chelerythrine chloride or PD98059. These results suggest that TMP can induce delayed cardioprotective effects by activation of protein kinase C and extracellular signal-regulated protein kinase 1/2 signalling pathways and subsequent increased expression of Hsp70 in rat neonatal cardiomyocytes. [source] Cardiovascular Protective Effects of ResveratrolCARDIOVASCULAR THERAPEUTICS, Issue 3 2004Silvia Bradamante ABSTRACT Resveratrol (3,4,,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans. [source] | |||||||||||||