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At least 865 records · Page 48Linked to original sources
PubMed1994

[Cytoprotective effect of neurotensin on acetaminophen induced liver injury in relation to glutathione system].

In the present work the cytoprotective effect of neurotensin (NT) on acetaminophen induced injury to the liver or cultured hepatocytes of mouse in relation to glutathione system were investigated. The results were as follows: Pretreatment with NT significantly reduced the leakages of transaminases induced by acetaminophen in vivo or in cultured hepatocytes and partially reversed the decline of DNA synthesis induced by acetaminophen in cultured hepatocytes. After administration of acetaminophen to cultured hepatocytes, the contents of reduced glutathione (GSH) and total glutathione decreased, the activity of glutathione peroxydase (GSH-Px) decreased, but the contents of oxidized glutathione (GSSG) showed no change. Pretreatment with NT before acetaminophen decreased the contents of GSH further but increased the contents of GSSG and total glutathione and enhanced the activity of GSH-Px. These results indicated that NT may enhance synthesis of glutathione and the ability for hepatocytes to scavenge free radicals by increasing the activity of GSH-Px accompanied by oxidation of GSH to GSSG.

Acetaminophen↗
PubMed1994

[Cytoprotective effects of nicorandil on immature myocytes under hypothermic conditions].

We evaluated the functional and biochemical effects of nicorandil on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days. Myocytes (12.5 x 10(5) myocytes/flask) were then incubated at 4 degrees C for 24 hrs in media with nicorandil as follows: O M nicorandil (group C: control), 10(-5)M (group N 1), 5 x 10(-5)M (group N 2), 10(-4)M (group N 3). After hypothermic incubation, CPK and LDH were measured. The myocytes were then cultured for 24 hrs at 37 degrees C to evaluate the recovery of myocyte beating rate. For the beating rate, group N 3 showed a significantly increased recovery compared to the control (N 3: 44.2, p < 0.02, C: 24.6 percent of control; ie, beating rate prior to hypothermic incubation). The release of CPK and LDH was significantly suppressed in group N 3 compared to the control (N 3: 24.1, p < 0.005, 247.2, p < 0.01; C: 125.4 mIU/flask, 459.5 mIU/flask, respectively). Thus, nicorandil has cytoprotective effects on immature myocytes under hypothermic conditions.

Animals↗
PubMed1994

Structure-activity relationship in the cytoprotective effect of helenalin and related compounds.

Our previous reports indicate that the cytoprotective effect of helenalin and several sesquiterpene lactones is mediated through a Michael reaction between the sulfhydryl containing peptides of the gastric mucosa and Michael acceptors present in the sesquiterpene lactone molecules. In the present work the different alternative active sites in molecules containing up to three places which could act as viable Michael acceptors are evaluated. To do this, an extensive conformational and electronic study of helenalin and its derivatives was carried out. The experimental and theoretical results obtained show the gamma-lactone and cyclopentenone groups to be the biologically active places of the molecules under study, whereas tiglic and angelic substituents in these compounds show different behavior as Michael acceptors.

Cardiotonic Agents↗
PubMed1994

[Cytoprotective effect of epidermal growth factor on acetaminophen induced acute injury of hepatocytes].

In the present work, the hepatoprotection of EGF was studied on an acetaminophen induced acute injury model of serum-free primary cultured mouse hepatocytes. The results were as follows: (1) When serum-free cultured mouse hepatocytes were exposed to acetaminophen (AAP 20 mmol/L) for 12-14 h, the activity of GPT and GOT were increased to a stable level, serving as a good hepatocyte injury model. (2) EGF of different doses (50, 100, 500, and 1000 ng/ml) added to the medium prior to acetaminophen could reduce hepatocyte injury in a dose-dependent manner. (3) Taking 3H-TdR incorporation as an index, it was observed that acetaminophen could reduce the DNA synthesis of hepatocytes, and pretreatment with EGF could reverse this effect, but, stimulation of DNA synthesis by EGF was not correlated with its hepatoprotection. Thus the reversion of the reduced DNA synthesis in EGF-pretreated hepatocytes is interpreted as the result rather than the cause of cytoprotection of the factor. (4) The hepatoprotection might be produced through affecting on the glutathione metabolism of hepatocytes.

Acetaminophen↗
PubMed1993

Lethal damage to endothelial cells by oxidized low density lipoprotein: role of selenoperoxidases in cytoprotection against lipid hydroperoxide- and iron-mediated reactions.

Oxidized low density lipoprotein (LDLox) is believed to be an important contributor to endothelial cytodamage and atherogenesis. The purpose of this study was to examine the role of glutathione (GSH) and GSH-dependent selenoperoxidases in cytoprotection against the damaging effects of LDLox. When irradiated in the presence of a phthalocyanine sensitizing dye, human LDL accumulated chromatographically detectable and iodometrically measurable lipid hydroperoxides (LOOHs). Photogenerated LDLox caused lethal damage to bovine aortic endothelial (BAE) cells in vitro, as determined by lactate dehydrogenase release and inhibition of thiazolyl blue reduction. When depleted of GSH by buthionine sulfoximine treatment, BAE cells became more sensitive to LDLox. Cells grown in 2% serum/DME-HAM's F-12 medium without added selenium [Se(-) cells] exhibited far lower GSH-peroxidase and phospholipid hydroperoxide GSH-peroxidase activities than selenium-supplemented controls [Se(+) cells], and were much more sensitive to oxidative injury induced by t-butyl hydroperoxide, liposomal cholesterol hydroperoxides, and LDLox. Preincubation of LDLox with GSH and Ebselen (a selenoperoxidase mimetic) resulted in a dramatic reduction in both LOOH content and cytotoxicity. Moreover, treating Se(-) cells themselves with Ebselen substantially restored their resistance to LDLox-induced damage. LDLox toxicity to Se(-) cells was strongly inhibited by desferrioxamine and stimulated by ferric-8-hydroxyquinoline (a lipophilic chelate), indicating that iron is an active participant in oxidative damage. These results demonstrate that the GSH-dependent selenoperoxidase(s) play(s) an important role in cellular defense against oxidized low density lipoprotein, presumably by detoxifying lipid hydroperoxides and thereby preventing their iron-catalyzed decomposition to damaging free radical intermediates.

Animals↗
PubMed1995

Comparative cytoprotection of cultured corneal endothelial cells by water-soluble antioxidants against free-radical damage.

We reported previously that purpurogallin (PPG) markedly protects the cultured rabbit corneal endothelial cells (RCEC) against oxyradical damage generated with hypoxanthine (HX) and xanthine oxidase (XO)(1). In this study, we further compared the cytoprotective activities of PPG versus Trolox (TX, alpha-tocopherol, a water-soluble analogue of vitamin E) and ascorbate (Asc) in confluent cultured RCEC with phase contrast microscopy and confirmed by transmission electron microscopy. PPG prolonged survival of the oxyradical damaged cells longer than those without PPG present (18.6 +/- 1.4 min at 1.0 mM and 11.2 +/- 1.0 at 0.25 mM respectively vs. 7.3 +/- 0.8 min in control). At levels equimolar to PPG, TX, and Asc were less effective in delaying cell necrosis caused by HX and XO (p < 0.01). When exposed to superoxide radicals generated by menadione, RCEC necrosed at 29.8 +/- 1.5 min compared to PPG 47.2 +/- 1.0 min at 1.0 mM and 38.9 +/- 1.0 min at 0.25 mM. This was significantly different from TX and Asc at corresponding concentrations (p < 0.01). PPG scavenges not only HX-XO-generated oxyradicals, but also nonenzymatically produced superoxide radicals, more actively than two well known antioxidants--TX and Asc.

Animals↗
PubMed1996

[Critical evaluation of factors influencing pancreatic cytoprotection].

The authors give a brief survey on adaptive pancreatic cytoprotection and vasoprotection in the framework of which noxious agents and factors of defensive mechanism are made known and critically evaluated. In development of acute pancreatitis intraacinar redistribution of lysosomal hydrolases, colocalization of digestive and lysosomal enzymes, escape of digestive and lysosomal enzymes from pancreatic ductal system into the interstitium, inflammatory modulators released from macrophages and evoking local inflammation, ischaemia, furthermore feedback regulation of pancreatic secretion can be regarded as motives. Factors of defensive mechanism include prostaglandins, nitric oxide and the unobstructed, juice flow which promote the repair of injured membranes in acinar and vascular endothelial cells, respectively. Their whole sum may be called adaptive pancreatic cyto- and vasoprotection or pancreatic "self-defence mechanism".

Acute Disease↗
PubMed1995

[The effect of selected cytoprotective drugs on alcohol-induced injury of isolated gastric mucosa cells].

There were performed experimental study on the effect of Al(OH)3, 16,16dmPGE2, indomethacin, verapamil and calcium ionophore A 23157 on alcohol-induced injury of isolated gastric mucosal cells of rat. In the first step a dose dependent alcohol injury of isolated gastric mucosal cells was shown. The most susceptible cells to alcohol damage were parietal cells. 16,16dmPGE2 and verapamil (calcium channel inhibitor), except Al(OH)3, were cytoprotective--they protected surface epithelial cells against alcohol. Indomethacin and calcium ionophore A 23157 (increases the calcium influx into the cell) aggravated the alcohol damage to gastric cells. The results show important role of prostaglandin and calcium ions in the mechanism of gastric mucosal cell damage and indicate the lack of direct influence of antacids on these cells in vitro, in conditions independent of microcirculation and neurohormonal factors.

Animals↗
PubMed1996

[Binding of epirubicin to human plasma protein and erythrocytes: interaction with the cytoprotective amifostine].

The in vitro binding rate of epirubicin (EPR) to different plasma proteins, control serum, red blood cells and whole blood was investigated without and with the cytoprotective agent amifostine. The binding rate of EPR to plasma proteins fractions and red blood cells dependend on the concentration of the matrix components. EPR was bound more than 90% to human serum alpha-globulin (alpha-HSG), to human serum albumine (HSA) and human serum beta-globuline (beta-HSG) at 80 to 90%, in the case of human serum gamma-globulin (gamma-HSG) the binding rate amounted 75%. The binding rate of EPR to RBCs in whole blood samples reached 38%. Within the observed concentration range of proteins (1-40 micrograms/ml, depending on the protein concentration) AMI caused a reduction of the protein-bound amount of EPR in the range from 2 to 19% of HSA, 4 to 20 in the case of beta-HSG, 2 to 32% in the case of alpha-HSG and 17 to 21% for gamma-HSG. In the whole blood samples the binding of EPR to proteins dropped from 45 to 32% and RBC-partitioning from 38 to 32%. Two compounds with free thiol groups, cystein and glutathione, were compared with AMI in regard to lowering the binding rate of EPR to HSA: the effect was exactly in the same order of magnitude: -17% for AMI, -21.0% for cystein and -20.8% for glutahion (p < 0.002). For a negative control, cystin and phenylalanin were tested, too: both compounds showed no influence on the protein binding of EPR: 63.8% binding rate in the control group, 65.2% in the presence of cystin and 64.6% in the presence of phenylalanin (statistically not significant). The present results indicate, that binding of EPR to serum proteins is reduced in the presence of AMI by interaction of the thiol-group with the protein and that the thiophosphoric ester bond in the test solution must cleave rapidly.

Amifostine↗
PubMed1997

The cytoprotective effect of iloprost against carbon tetrachloride induced necrosis in rat liver.

The aim of this study was to investigate the cytoprotective effect of Iloprost on the liver against carbon tetrachloride induced necrosis. The serum histamine-like activity was found to be increased when compared with that of controls after treatment with carbon tetrachloride for 18 weeks while prostaglandin E2- and leukotriene C4-like activities were unchanged. After pretreatment with Iloprost for 18 weeks the increased activity of histamine was found to be unchanged while prostaglandin E2-like activity was increased. It is concluded that Iloprost protects the liver against carbon tetrachloride-induced damage and reduces the level of histamine that has a role in the pathogenesis of portal hypertension.

Animals↗
PubMed1997

Gastric anti-ulcer and cytoprotective effect of l-serine in rats.

Effect of l-serine has been studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against stress and chemically induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without l-serine treatment. Experimental gastric lesions were induced by hypothermic-restraint stress, indomethacin and necrotizing agents including 80% ethanol, 0.2 M sodium hydroxide and 0.6 M hydrochloric acid in rats. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that l-serine produces a dose-dependent inhibition of gastric acid secretions in rats. Pretreatment with l-serine also attenuated the formation of stress-, indomethacin- and necrotizing agents-induced gastric lesions. The antiulcer activity of l-serine was associated with significant inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. In conclusion, this study demonstrates that l-serine possesses significant antiulcer and cytoprotective activity against various experimentally induced gastric lesions. Although the mechanism of action of l-serine requires further evaluation, the experimental observations derived from this study may have future clinical relevance and therefore deserve to be investigated thoroughly.

Animals↗
PubMed1997

Studies on the antisecretory, gastric anti-ulcer and cytoprotective properties of glycine.

Glycine, a neutral amino acid has been studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without glycine treatment. Experimental gastric lesions were induced by hypothermic-restraint stress, indomethacin and necrotizing agents including 80% ethanol, 0.2 M sodium hydroxide and 0.6 M hydrochloric acid in rats. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that glycine dose dependently reduced the gastric secretions in rats. Pretreatment with glycine significantly protected animals against stress-, indomethacin- and necrotizing agents induced gastric lesions. The antiulcer activity of glycine was associated with significant inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. In conclusion, this study demonstrates that glycine possesses significant antiulcer and cytoprotective activity. However, further detailed studies are warranted to establish the mechanism(s) of action, and to determine its role in the prophylaxis and treatment of gastric ulcer disease.

Animals↗
PubMed1998

Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases.

Overexpression of heat shock protein 70 kDa alters the susceptibility of tumor cells to chemotherapeutic agents. We conducted experiments to study the regulation of expression of heat shock proteins (HSPs) in heat shock-treated T47-D cells, a human breast cancer cell line that expresses estrogen receptors. Cells exposed to heat shock at 44 degreesC displayed increased expression of heat shock protein 72 kDa (HSP-72), glucose-regulated protein 78 kDa (GRP-78), and GRP-94 in a time-dependent manner, as shown by [35S]methionine incorporation and Western blotting experiments. The maximal rate of synthesis occurred between 2 and 4 h after heat shock. Removal of external Ca2+ inhibited the synthesis of the heat shock-induced GRP-78 but not of HSP-72 and GRP-94, whereas treatment of cells with BAPTA (a Ca2+ chelator) inhibited HSP-72 and GRP-78. Treatment with H89 (a protein kinase A inhibitor) blocked the heat shock-induced GRP-78 synthesis, whereas GF-109203X (a protein kinase C inhibitor) attenuated the heat shock-induced HSP-72 synthesis and completely blocked synthesis of GRP-78 but not of GRP-94. These results indicate that protein kinase C is involved in regulation of the heat shock-induced synthesis of HSP-72, whereas PKA and PKC are involved in the regulation of GRP-78 synthesis. Cells overexpressing HSP-72 and GRPs after heat shock displayed resistance against lethal temperature (47 degreesC for 50 min) -induced death, which was diminished after removal of external Ca2+ and treatment with GF-109203X. Heat shock increased intracellular free Ca2+ concentration ([Ca2+]i) in a temperature- and heating duration-dependent fashion, and the increase was inhibited in the absence of external [Ca2+]i and significantly reduced by pretreatment with H89 and GF-109203X. The results suggest that different pathways are involved in the induction of synthesis of HSP-72, GRP-78, and GRP-94 by heat shock. It is highly likely that only HSP-72 and GRP-78 are involved in the process of cytoprotection from the thermal injury.

Calcium↗
PubMed2000

Cytoprotection does not preserve brain functionality in rats during the acute post-stroke phase despite evidence of non-infarction provided by MRI.

In animal models of stroke the promise of a therapy is commonly judged from infarct size measurements, assuming that a reduction in infarct size results in reduction of the functional deficits. We have evaluated the validity of the concept that structural integrity translates into functional integrity during the acute post-stroke period (24 h). Unilateral permanent middle cerebral artery occlusion (pMCAO) in Fischer F344 rats leads to infarcts comprising the ipsilateral striatum and cortical structures, including the somatosensory cortex. Infarct volumes were assessed using magnetic resonance imaging (MRI) methods (T(2), diffusion, perfusion MRI). The functional integrity of the somatosensory cortex was assessed by functional MRI (fMRI) measuring changes in local cerebral blood volume, and by assessing the forelimb grip strength and the beam-walking performance of the animals. Treatment with the calcium antagonist isradipine (2.5 mg/kg injected s.c. immediately after pMCAO) reduced the total infarct size by more than 40% compared to vehicle-injected controls. In particular, the ipsilateral somatosensory cortex appeared normal in diffusion- and T(2)-weighted MRI images. In sham-operated rats simultaneous electrical stimulation of both forepaws led to similar activation of both somatosensory cortices, while in pMCAO animals given vehicle only the contralateral cortex showed an fMRI response. Similarly, in pMCAO rats treated with isradipine, functional activation following bilateral electrical stimulation was only detected in the contralateral somatosensory cortex despite the normal appearance of the ipsilateral cortex in MRI images. Furthermore, fMRI responses to pharmacological stimulation with bicuculline were virtually absent in the ipsilateral somatosensory cortices both in vehicle- and isradipine-treated rats. Finally there was no significant difference between vehicle- and isradipine-treated animals upon the performance of beam-walking test or in forelimb grip strength. It is concluded that during the acute (24 h) post-occlusion period, structural integrity in the somatosensory cortex revealed by MRI does not translate into preservation of function.

Adenosine Triphosphate↗
PubMed2007

The influence of extremely low frequency magnetic fields on cytoprotection and repair.

Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

Analgesics, Opioid↗
PubMed2003

Cytoprotective and anticancer properties of coenzyme Q versus capsaicin.

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and serves as an electron donor and acceptor in mitochondrial energy-linked respiration. CoQ1 was shown to prevent ROS formation and cell death in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ1 inhibited ROS formation but CoQ1 was more effective at restoring the mitochondrial membrane potential collapse caused by complex 1 inhibitors such as rotenone. At low concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. Lipid peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and CoQ1 became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse of the mitochondrial membrane potential, however, only capsaicin caused ROS formation. The capsaicin side chain was required for capsaicin induced cytotoxicity. The anticancer properties of CoQ1 and capsaicin should prove useful for inducing tumor cell apoptosis.

Animals↗
PubMed2005

Cytoprotection against oxidative stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors.

Oxidative stress is the main cause of neuronal damage in traumatic brain injury, hypoxia/reperfusion injury, and neurodegenerative disorders. Although extracellular nucleosides, especially adenosine, are well known to protect against neuronal damage in such pathological conditions, the effects of these nucleosides or nucleotides on glial cell damage remain largely unknown. We report that ATP but not adenosine protects against the cell death of cultured astrocytes induced by hydrogen peroxide (H2O2). ATP ameliorated the H2O2-induced decrease in cell viability of astrocytes in an incubation time- and concentration-dependent fashion. Protection by ATP was inhibited by P2 receptor antagonists and was mimicked by P2Y1 receptor agonists but not by adenosine. The expressions of P2Y1 mRNAs and functional P2Y1 receptors in astrocytes were confirmed. Thus, ATP, acting on P2Y1 receptors in astrocytes, showed a protective action against H2O2. The astrocytic protection by the P2Y1 receptor agonist 2-methylthio-ADP was inhibited by an intracellular Ca2+ chelator and a blocker of phospholipase C, indicating the involvement of intracellular signals mediated by Gq/11-coupled P2Y1 receptors. The ATP-induced protection was inhibited by cycloheximide, a protein synthesis inhibitor, and it took more than 12 h for the onset of the protective action. In the DNA microarray analysis, ATP induced a dramatic upregulation of various oxidoreductase genes. Taken together, ATP acts on P2Y1 receptors coupled to Gq/11, resulting in the upregulation of oxidoreductase genes, leading to the protection of astrocytes against H2O2.

Adenosine Triphosphate↗