Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cytoprotection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,711 records · Page 95Linked to original sources
PubMed2002

Developmental changes in inhibitory effects of arsenic and heat shock on growth of pre-implantation bovine embryos.

Although sensitive to various disrupters, pre-implantation embryos possess some cellular cytoprotective mechanisms that allow continued survival in the face of a deleterious environment. For stresses such as heat shock, embryonic resistance increases as development proceeds. Present objectives were to determine whether (1) arsenic compromises development of pre-implantation bovine embryos, (2) developmental changes in embryonic resistance to arsenic mimic those seen for resistance to heat shock, and (3) developmental patterns in induction of apoptosis by arsenic are correlated with similar changes in resistance of embryos to inhibitory effects of arsenic on development. Bovine embryos produced by in vitro fertilization were exposed at the two-cell stage or at day 5 after insemination (embryos > or = 16-cells in number) to either sodium arsenite (0, 1, 5, or 10 microM) or heat shock (exposure to 41 degrees C for 0, 3, 4.5, 6, or 9 hr). Arsenic induced apoptosis and increased group 2 caspase activity for embryos at the > or = 16-cell stage, but not for embryos at the two-cell stage. In contrast to these developmental changes in apoptosis responses, exposure to arsenic reduced cell number 24 hr after exposure for both two-cell embryos and embryos > or = 16-cells. Similarly, the percentage of embryos that developed to the blastocyst stage at day 8 after fertilization was reduced by arsenic exposure at both stages of development. Heat shock, conversely, reduced development to the blastocyst stage when applied at the two-cell stage, but not when applied to embryos > or = 16-cells at day 5 after insemination. In conclusion, arsenic can compromise development of bovine pre-implantation embryos, the temporal window of sensitivity of embryos to arsenic is wider than for heat shock, and cellular cytoprotective responses that embryos acquire for thermal resistance are not sufficient to cause increased embryonic resistance to arsenic exposure. It is likely that despite common cellular pathologies caused by arsenic and heat shock, arsenic acts to reduce development in part through biochemical pathways not activated by heat shock. Moreover, the embryo does not acquire significant resistance to these perturbations within the time frame in development examined.

Animals↗
PubMed1995

Evaluation of protective effects of prostaglandin E1 on ischemic liver damage with in vivo 31P-MR spectroscopy.

The cytoprotective effect of prostaglandins (PG) was evaluated by in vivo 31P MR spectroscopy. Twenty rabbits were divided into two groups; the control group given physiological saline, and the PG group given prostaglandin E1 (0.5 microgram/kg/min). Each solution was infused for 8 min, after which complete hepatic ischemia was induced for 20 min, followed by reperfusion for 40 min. During ischemia, beta-ATP decreased to 23.6% and 42.3%, phosphomonoester increased to 260% and 200% of their initial values in the control and the PG groups, respectively. Inorganic phosphate also increased. After reperfusion, beta-ATP recovered to 65.2% and 96.5%, phosphomonoester to 130% and 110%, inorganic phosphate to 140% and 120% in the control and PG groups, respectively. The changes during ischemia were significantly smaller and the recoveries during reperfusion were more complete in the PG group. These results may confirm the cytoprotective effect of prostaglandins by in vivo 31P-MR spectroscopy.

Adenosine Triphosphate↗
PubMed2004

Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part II. caffeic, chlorogenic and rosmarinic acids.

The chemoprotective effects of caffeic (CA), chlorogenic (CHA) and rosmarinic (RA) acids were tested against the toxicity of doxorubicin (DOX) in neonatal rat cardiomyocytes and the iron-dependent DOX induced lipid peroxidation of heart membranes, mitochondria and microsomes. The protectivity of these acids was compared with dexrazoxan, used as an adjuvant during DOX chemotherapy. The cytoprotective effects were assessed by enzyme (LDH and ASAT) and troponin I leakage, secondly by intracellular ATP content. All hydroxycinnamic acids proved non-cytotoxic, and they stabilized both membranes and the energetic status of cardiomyocytes. After preincubation of cardiomyocytes with the test compounds (100, 200 microm; 1 h) the cardiomyocytes were treated with the toxic agent, DOX (100 microm; 8 h). The test compounds protected cardiomyocytes against DOX induced oxidative stress (RA > CHA > or = CA) on all monitored parameters. Substantial preservation of monolayer integrity of the cardiomyocytes by test compounds was also found microscopically. All the acids were more effective in the assays used than dexrazoxan. RA showed the most effective cytoprotectivity. All the acids significantly reduced the iron-dependent DOX induced lipid peroxidation of heart membranes, although of the test compounds, CHA was found to be the most effective (IC(50) = 8.04 +/- 0.74/6.87 +/- 0.52 micro m for microsomes/mitochondria).

Animals↗
PubMed2006

Protective effect of selected flavonoids on in vitro daunorubicin-induced cardiotoxicity.

Flavonoids are an ubiquitous group of polyphenolic substances with varied chemical structures present in foods of plant origin and act as free radical scavenging and chelating agents with a variety of biological activities. Using a model of spontaneously beating, cultured adult rat cardiomyocytes, this study examined the cardioprotective role of quercetin, naringenin, pycnogenol and a model antioxidant, trolox, against daunorubicin-induced toxicity. Cardiomyocyte protection was assessed by MTT test and extracellular lactate dehydrogenase detection. Protection of cardiomyocytes was concentration/dose dependent for quercetin > naringenin > pycnogenol > trolox. Quercetin (10(-4)-10(-6) mol/L) after 24 h of co-incubation with daunorubicin significantly increased the cardiomyocyte survival in all tested concentrations (p < 0.001). The cytoprotective effect of naringenin (10(-4)-10(-6) mol/L) was similar to those of quercetin (p < 0.001 and p < 0.01, respectively). Pycnogenol was the least effective of the flavonoids studied. On the other hand, all tested flavonoids had significantly better protective effects than trolox. The leakage of lactate dehydrogenase induced by daunorubicin was also prevented by the studied compounds and was in accordance with their cytoprotective activity.

Animals↗
PubMed1994

Adenosine acts as an endogenous activator of the cellular antioxidant defense system.

Oxygen free radicals have been implicated in the pathogenesis of ischemic cell injuries. These free radicals are normally scavenged by antioxidant enzymes. Adenosine is normally released during ischemia and protects against ischemic injuries by interacting with adenosine receptors (ARs). The mechanism underlying its cytoprotective action is unclear. In this report, we provide evidence that activation of a unique A3AR in rat basophilic leukemia cells (RBL-2H3) leads to a 2 to 3 fold increase in activity of superoxide dismutase, catalase and glutathione peroxidase and also increases in the activity of glutathione reductase. Similar increases in enzyme activity were elicited in bovine and human endothelial cells, rat cardiac myocytes and smooth muscle cells. Increases in enzyme activity were attenuated by theophylline (an antagonist of the A3AR) and by pertussis toxin, implicating a role of A3AR/Gi protein in the activation. Importantly, activation of the A3AR decreased the degree of lipid peroxidation in these cells. These data provide strong evidence that the cytoprotective action of adenosine during ischemic cell injuries is mediated, at least in part, via a novel mechanism-activation of the cellular antioxidant enzymes.

Adenosine↗
PubMed1998

Cyclic AMP mediates endothelial protection by nitric oxide.

Incubation with TNF-alpha (50 ng/ml) for 72 hours markedly reduced viability of endothelial cells. A 6-hour preincubation with S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-100 microM) protected cells in a concentration-dependent manner and decreased TNF-alpha-mediated toxicity by up to 70%. Cytoprotection by SNAP was completely abolished by the adenylyl cyclase inhibitor 2', 5'-dideoxyadenosine and mimicked by 8-bromo cyclic AMP or forskolin. SNAP produced significant increases in cyclic GMP and cyclic AMP, both being abrogated in the presence of the NO scavenger 2-phenyl-4, 4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Moreover, no endothelial protection by SNAP was detected in the presence of the protein kinase A inhibitor KT5720, whereas the protein kinase G inhibitor KT5823 left cytoprotection virtually unaltered. Our results demonstrate a crucial role for cyclic AMP in mediating NO-induced endothelial protection against TNF-alpha, possibly through cyclic GMP-dependent inhibition of cyclic AMP breakdown. NO-dependent endothelial protection may ultimately result from cyclic AMP-induced up-regulation of antioxidant proteins or down-regulation of cytotoxic processes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Inhibition of Na,K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells.

In the present study we used LLC-PK1 cells, a porcine renal proximal tubular cell line, to investigate whether PI3 kinase activation was involved in the anti-apoptotic effect of ouabain, a specific inhibitor of Na,K-ATPase. Apoptosis was induced by actinomycin D (Act D, 5 microM) and assessed by appearance of hypodiploid nuclei and DNA fragmentation. Ouabain attenuated Act D-induced apoptotic response in a dose-dependent manner. Incubation in a low K(+) medium (0.1 mM) which is another way to decrease Na,K-ATPase activity also had anti-apoptotic effect. Both ouabain and low K(+) medium increased the PI3 kinase activity in p85 immunoprecipitates. Ouabain, as well as incubation in the low K(+) medium, also increased the phosphorylation of Akt. Inhibition of PI3 kinase by either wortmannin or LY294002 reversed the cytoprotective effect of ouabain. These data together indicate that inhibition of Na,K-ATPase activates PI3 kinase in LLC-PK1 cells which could then exert the cytoprotective effect.

Animals↗
PubMed1999

Enhanced oxygen delivery reverses anaerobic metabolic states in prolonged sandwich rat hepatocyte culture.

It must be assumed that current petri dish primary hepatocyte culture models do not supply sufficient amounts of oxygen and thus cause anaerobic metabolism of the cells. This is contrary to the physiologic state of the cells. In vivo the liver is a highly vascularized organ with a rather high blood flow rate of a mixture of arterial and venous blood. The aim of the present study was to show the oxygen dependence of primary rat hepatocytes in long-term culture and to define appropriate conditions that could allow hepatocytes to maintain tissue specific functions in an aerobic environment. To this purpose matrix overlaid hepatocytes were either cultured on gas-permeable (fluorinated hydrocarbon films) or gas-impermeable (polystyrene) supports at 10% and 20% ambient oxygen concentration (v/v), respectively. Tissue-specific functions were assessed by studying albumin and urea secretion as well as xenobiotic metabolism. The mRNA expression and catalytic activities of the cytoprotective antioxidant enzymes mitochondrial manganese superoxide dismutase (MnSOD), cytosolic copper and zinc superoxide dismutase, peroxisomal catalase, and cytosolic glutathione peroxidase were investigated to assess intracellular responses to the defined variations in oxygen supply. Hepatocytes could successfully be maintained at aerobic conditions in long-term culture on gas-permeable PTFE films. At 50% (10%, v/v) of currently used oxygen levels lactate accumulation was prevented, a plateau-like albumin secretion reestablished, urea secretion improved, and xenobiotic metabolism proceeded at physiological rates. mRNA expression of cytoprotective enzymes responded to the pericellular availability of oxygen and was most pronounced in the case of MnSOD. However, the biggest stress factor for the hepatocytes still appeared to be the isolation procedure, as mRNA expression and catalytic activities were most elevated shortly thereafter. In conclusion, this study clearly shows the oxygen dependence of primary rat hepatocytes in long-term culture and indicates means to establish appropriate conditions for the aerobic culture of primary rat sandwich hepatocytes with full maintenance of function. The long-term culture of hepatocytes on oxygenating supports at in vivo-like oxygen tensions therefore appears to be more physiologic and beneficial for the cells.

Aerobiosis↗
PubMed2002

Antioxidant and lysosomotropic properties of acridine-propranolol: protection against oxidative endothelial cell injury.

The antioxidant and lysosomotropic properties of a fluorescent analogue of propranolol, 9-amino-acridine-propranolol (9-AAP) were compared to those of propranolol. Using isolated microsomal membranes exposed to a superoxide and hydroxyl radical generating system, 9-AAP was found to be at least 10-fold more potent than propranolol (and about 50% as potent as vitamin E) in inhibiting lipid peroxidation. In cultured endothelial cells, 9-AAP afforded moderate protective effect against acute loss of glutathione but potent cytoprotective activity against free radical-mediated loss of viability/survival. Intracellular localization of 9-AAP was examined by fluorescent microscopy and compared with two known fluorescent lysosomal markers: acridine orange and Lysosensor. All three agents appeared to localize to similar peri-nuclear vesicles, presumably lysosomes or pre-lysosomes. Lysosensor fluorescence was not observable in the presence of 9-AAP, foreclosing the possibility of a direct dual labeling experiment. We employed the pH sensitivity of acridine orange to determine if it labels the same vesicles as 9-AAP. When the endothelial cells were preloaded with acridine orange, washed and resuspended in buffer containing 9-AAP, the dark orange-labeled vesicles observed with acridine orange alone became increasingly lighter with time. Since the fluorescence of acridine orange is altered by pH change, this spectral shift in fluorescence emission is consistent with the indication that added propranolol (or the analog) leads to lysosomal alkalization. In conclusion, 9-AAP is both a strong antioxidant and a lysosomotropic agent that is remarkably insensitive to photobleaching. These properties may contribute to the enhanced endothelial cytoprotective effects against free radical-induced injury.

Animals↗
PubMed1996

Effects of polyunsaturated fatty acids on bile acid-induced gastric mucosal injury.

Arachidonic acid is a polyunsaturated fatty acid precursor to prostaglandin formation in the stomach. When applied topically to gastric mucosa it prevents injury from a variety of damaging agents, similar to the effects observed with exogenous prostaglandins. Alternatively, fatty acids could act as mild irritants and protect the gastric mucosa in an adaptive cytoprotective process. This study was undertaken to ascertain whether arachidonic acid attenuates gastric injury from bile acid by acting as a mild irritant to the gastric epithelium or by increasing biosynthesis of cytoprotective prostaglandins. Accordingly, adult anesthetized rat stomachs were pretreated for 30 min with either topical 1 mM arachidonic acid, docusahexaenoic acid or eicosatrienoic acid prior to injury with topical 5 mM acidified taurocholate. In a second set of experiments using a similar protocol, the role of prostaglandins was evaluated by giving indomethacin (5 mg/kg/sc) 30 min prior to fatty acid pretreatment. Mucosal injury was assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology. Gastric luminal PGE2 content was determined by radioimmunoassay. Pretreatment with topical arachidonic acid, but not docusahexaenoic acid or eicosatrienoic acid, significantly (P < 0.05) decreased bile acid induced net luminal ion fluxes, DNA accumulation and histologic injury scores, an effect negated by indomethacin. Further, pretreatment with arachidonic acid was associated with increased luminal PGE2 content, an effect also abolished by indomethacin. Thus, arachidonic acid does not act as a mild irritant, but protects the gastric mucosa from bile acid injury through a mechanism involving increased bio-availability of substrate for prostaglandin formation.

Animals↗
PubMed1998

Nitric oxide inhibits peroxide-mediated endothelial toxicity.

BACKGROUND: Oxidant molecules and nitric oxide (NO) have each been implicated as mediators of endothelial cell damage, but the biologic effect of these molecules acting in concert is incompletely understood. MATERIALS AND METHODS: We studied the effects of an NO donor, S-nitroso-acetyl-D,L-penicillamine (SNAP), in combination with the peroxidants tert-butyl hydroperoxide (TBH) and hydrogen peroxide (H2O2) on rabbit aortic endothelial cells in culture. Cell viability was assessed using Alamar blue, a nontoxic dye indicator of cell metabolism. Lipid peroxidation was assessed using a chemiluminescent single-photon counting technique. RESULTS: After 90 min exposure to test reagents, there was concentration-dependent cytotoxicity for both TBH and H2O2. Peroxidant-induced cytotoxicity was significantly ameliorated by SNAP (10(-4)-10(-3)M). N-Acetylpenicillamine and NO-depleted SNAP failed to demonstrate a cytoprotective effect against peroxidant cellular injury, thus implicating NO as the agent responsible for the protective effect. SNAP reduced lipid peroxidation caused by 10(-3) M TBH in a dose-dependent manner. Preincubation of cells with SNAP before exposure to peroxidants alone had no effect on toxicity. CONCLUSIONS: NO is cytoprotective to the endothelium in the presence of peroxidants through a reduction of lipid peroxidation.

Animals↗
PubMed2002

Heparin-binding EGF-like growth factor down regulates proinflammatory cytokine-induced nitric oxide and inducible nitric oxide synthase production in intestinal epithelial cells.

We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) protects intestinal epithelial cells (IEC) from necrosis and apoptosis in vitro and from intestinal ischemia/reperfusion injury in vivo; however, the mechanisms of HB-EGF cytoprotection are unclear. Overproduction of iNOS and NO have been implicated in the pathogenesis of several forms of ischemia/reperfusion injury. We therefore studied whether HB-EGF could down-regulate proinflammatory cytokine-induced iNOS and NO production in intestinal epithelial cells in vitro. DLD-1 human intestinal epithelial cells were exposed to the proinflammatory cytokines interleukin-1beta (IL-1beta) (20 ng/ml) and interferon-gamma (IFN-gamma) (10 ng/ml) to stimulate iNOS induction and NO production. Cells were treated with HB-EGF (0-100 ng/ml) either before or with cytokine exposure, and cells and supernatants were harvested 24 and 48 h later. Accumulated NO was measured in supernatants by chemiluminescence. Total RNA was extracted from cell lysates for iNOS mRNA quantification using real-time reverse transcription-polymerase chain reaction (RT-PCR), and total protein was extracted from cell lysates for detection of iNOS protein. HB-EGF significantly decreased cytokine-induced NO production in a dose dependent manner, and NO reduction was associated with iNOS suppression at both the mRNA and protein levels. While cytokine exposure resulted in a significant increase in iNOS mRNA expression in these cells (109 plus minus 9 fold), HB-EGF reduced iNOS expression by 5.7-fold (P < 0.05). These results suggest that HB-EGF may exert its cytoprotective effects, in part, by down-regulating iNOS and NO production, and provides further rationale for additional testing of the effects of HB-EGF in the treatment of intestinal ischemia/reperfusion injury in vivo.

Antibodies↗
PubMedDate not supplied

Effect of DL alpha-lipoic acid on tissue lipid peroxidation and antioxidant systems in normal and glycollate treated rats.

The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decrease in catalase activity and glutathione (GSH) level, are the salient features observed in tissues of hyperoxaluric rats. Free radical toxicity in the glycollate fed rats is effectively counteracted by lipoic acid administration. Lipoic acid administration brought about a significant decrease in peroxidative levels with an increase in catalase activity and glutathione level. These observations highlight the antioxidant property of alpha-lipoic acid and its cytoprotective action against experimental hyperoxaluria.

Animals↗
PubMed1999

Prevention of ethanol-induced gastric lesions in rats by natural honey and glucose-fructose-sucrose-maltose mixture.

The cytoprotective properties of various natural honey specimens and of a glucose-fructose-sucrose-maltose mixture (GFSM) against gastric ethanol-induced lesions have been evaluated in rats. GFSM mixture and honey (2.5 g kg-1) were given orally 30 min before administration of 100% ethanol (5 ml kg-1) for a further 15-min period. Animal pretreatment with GFSM or honey prevented the formation of gastric lesions. The number and severity of haemorrhagic lesions were reduced by 98%. Stomach acid content increased by 110-703% according to honey specimens. The similar protective effects of honey and GFSM mixture suggest that carbohydrates at high concentrations behave as mild irritants that can induce adaptive cytoprotection.

Animals↗
PubMed2001

Lazaroid compounds prevent early but not late stages of oxidant-induced cell injury: potential explanation for the lack of efficacy of lazaroids in clinical trials.

Earlier in vitro studies demonstrated the remarkable potency of the lazaroid compounds to prevent oxidant-induced early cell injury. However, the ability of lazaroid compounds to limit oxidative injury in vivo(including renal ischemia-reperfusion) has been less certain, and the early clinical trials using lazaroids to limit CNS injury or organ injury in the setting of transplantation have not been promising. Lazaroid compounds are potent inhibitors of lipid peroxidation, and their inability to influence other key injury processes, particularly during the late stages of cell injury, might partly explain the limited clinical efficacy. To test this, renal tubular (LLC-PK1) cells were incubated with 250 micromH(2)O(2)for 135 min, in the presence or absence of 2-methyl aminochroman (2-MAC, U-83836E), a lazaroid with potent ability to inhibit lipid peroxidation, or desferrioxamine, (DFO) an iron chelator with broader antioxidant efficacy. Cell injury, lipid peroxidation, DNA damage and ATP depletion were measured in the early (immediately after H(2)O(2)incubation) and late (24 h after H(2)O(2)incubation) stages of cell injury. In the early stage, 2-MAC suppressed H(2)O(2)-induced lipid peroxidation and LDH release, but not the DNA damage, ATP depletion or loss of cell replication. In contrast, DFO suppressed all of the measurements. In the late stages, despite continued suppression of lipid peroxidation, only DFO maintained significant cytoprotection against H(2)O(2), and this was accompanied by reduced DNA damage, higher ATP levels and preservation of cell proliferation. Thus, the inability of the lazaroid compound 2-MAC to sustain cytoprotection in the later stages of cell injury might provide at least a partial explanation for the inefficiency of lazaroids to limit tissue injury in clinical and certain in vivo settings.

Adenosine Triphosphate↗
PubMed1992

Alpha-methyl-para-tyrosine pretreatment protects from striatal neuronal death induced by four-vessel occlusion in the rat.

Rats were treated with alpha-methyl-para-tyrosine (AMT, 250 mg/kg, i.p), an hydroxylase inhibitor, in order to decrease brain levels of catecholamines. Six hours later, when cerebral dopamine (DA) and norepinephrine were reduced by about 80%, a transient forebrain ischemia of 30 min duration was induced by four-vessel occlusion technique. Evaluation of brain damage 72 hours after ischemia showed that AMT treatment significantly decreased neuronal necrosis in the striatum but had no cytoprotective effect in the CA1 sector of the hippocampus and in the neocortex. AMT treatment reduced mortality within the ischemic period but did not affect either the mortality within the recirculation period or the postischemic neurologic deficit. These results suggest that the striatal cytoprotective effect of AMT is linked to cerebral DA depletion and that excessive release of DA during ischemia or dopaminergic hyperactivity during recirculation play a detrimental role in the development of ischemic cell damage in the striatum.

Animals↗
PubMed1997

Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole.

The direct-acting dopamine (DA) agonist pramipexole (2 amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochlori de) was evaluated for its ability to attenuate levodopa-induced loss of tyrosine hydroxylase immunoreactive (THir, a marker for dopamine neurons) cells in mesencephalic cultures. Pramipexole reduced levodopa-induced THir cell loss in a dose-dependent and saturable fashion (ED50 = 500 pM), its inactive stereoisomer was significantly less potent in this regard and pergolide and bromocriptine had negligible cytoprotective effects. Culture media from mesencephalic cultures incubated with pramipexole for 6 days increased THir cell counts in freshly harvested recipient cultures. The magnitude of this effect was directly proportional to the amount of pramipexole in the donor cultures and heat-inactivation of the media abolished the growth promoting effect. The results from this exploratory set of experiments suggest that pramipexole may be cytoprotective to dopamine neurons in tissue culture. Pramipexole's affinity for DA receptors, its antioxidant action or its ability to enhance mesencephalic trophic activity could be responsible for this effect.

Animals↗
PubMed1982

Effect of increased gastric mucosal histamine on alcohol-induced gastric damage in rats.

The aim of this study was to determine whether the cytoprotective effect of prostaglandin might be mediated, at least in part, by inhibition of intramucosal histamine release. Intragastric instillation of increasing concentrations of ethanol in 150 mM HCl resulted in increasing lesion scores and increasing histamine release into the gastric content. Pretreatment with 16,16-dimethyl prostaglandin E2 significantly reduced both lesion scores and gastric histamine output. The intragastric instillation of histamine with tracer [14C]histamine either with or after 50% ethanol resulted in significant gastric tissue uptake of histamine and increased acid secretion. However this had no effect on lesion score, protein output or the protective effect of prostaglandin pretreatment. We conclude that the cytoprotective effect of 16,16-dimethyl prostaglandin E2 in the rat is independent of intramucosal histamine release.

Animals↗