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At least 1,153 records · Page 64Linked to original sources
PubMed1990

The cytoprotective effect of Trolox demonstrated with three types of human cells.

Trolox, a hydrophilic analogue of alpha-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocyte against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2'-azo-bis(2-amidinopropane) HCl). Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes.

Antioxidants↗
PubMed1982

Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study.

Acute haemorrhagic erosions were produced in chambered gastric mucosae of rats by infusion into the chamber of 40% ethanol (v/v) for 10 min, followed by 50 mM HCl for 1 h. This procedure produced erosions which extended over nearly 70% of the glandular mucosa. When one of 2% ethanol, prostaglandin E2 (75 micrograms/kg in either 2% ethanol or in aqueous solution), or isoproterenol (50 micrograms/kg) was placed in the chamber for 10 min prior to infusion of 40% ethanol, the resultant lesions were significantly reduced in area (mean lesion area 25-31% of the glandular mucosa). When compared with the effects of 40% ethanol without pretreatment, there was no consistent correlation between pretreatment with these agents and changes in mucosal potential difference (PD) or net fluxes of Na+ and H+. All of the pretreatment groups did show a reduced loss of Cl from the chamber in the final 10-min period of the experiments. Exposure to the "protective" agents did not result in qualitative changes in mucosal structure at either the light or electron microscopic levels. Rather, the ultimate effect of pretreatment was to reduce the extent of deep mucosal vasocongestion. The reduction in lesion area could be directly related to these reductions in vasocongestion and not to any enhanced resistance of the luminal epithelium to the damaging effects of 40% ethanol.

Animals↗
PubMed1994

Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol.

The present study determined the effects of nitric oxide (NO) synthase induction on ethanol-mediated damage to rat gastric mucosa. NO synthase activity was determined by [14C]arginine conversion to radiolabeled citrulline. Ca(2+)-independent NO synthase activity was determined by citrulline formation in the presence of EGTA (1 mM) in the incubation mixture. Intraluminal ethanol administration (2 mL; 40% w/v) to control rats resulted in an increase in mucosal damage characterized as vasocongestion and hemorrhagic necrosis and a reduction in Ca(2+)-dependent NO synthase activity. Administration of Escherichia coli lipopolysaccharide (LPS; 3 mg/kg i.v.) augmented Ca(2+)-independent NO synthase activity (determined 4 h later) and reduced damage in response to intraluminal ethanol instillation. Ethanol treatment did not significantly affect induction of NO synthase activity. Dexamethasone pretreatment (1 mg/kg i.v. 2 h before LPS administration) reduced both Ca(2+)-independent NO synthase activity and the gastroprotective effect of LPS against ethanol-mediated mucosal injury. Likewise, concurrent administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.) inhibited the gastroprotection associated with LPS treatment, an effect abolished by pretreatment with the NO substrate L-arginine (300 mg/kg s.c.). Indomethacin (5 mg/kg i.v.) was ineffective in suppressing LPS-mediated gastroprotection. These results suggest that while Ca(2+)-dependent NO formation is inhibited by ethanol treatment, the inducible Ca(2+)-independent NO synthase plays a role in LPS-mediated gastroprotection against ethanol-mediated damage to the gastric mucosa.

Amino Acid Oxidoreductases↗
PubMed1996

NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium.

We investigated the effect of nitric oxide (NO) on the induction of the stress protein heme oxygenase and its protective role in vascular endothelial cells exposed to hydrogen peroxide. Treatment of porcine aortic endothelial cells for 6 h with the NO-releasing compounds (0.1-1 mM) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) resulted in a concentration-dependent increase in heme oxygenase activity. At 1 mM, the activity of heme oxygenase was augmented 8.5-fold with SNP, 5.8-fold with SNAP, and 5.7-fold with SIN-1 over the control value. In contrast, endothelial cells exposed to 100 microM S-bromoguanosine 3',5'-cyclic monophosphate, a tissue-permeable analogue that mimics the action of guanosine 3',5'-cyclic monophosphate, did not show any change in heme oxygenase activity. Activation of the inducible NO synthase by the synergistic action of bacterial lipopolysaccharide (250 ng/ml) and interferon-gamma (100 U/ml) also increased endothelial heme oxygenase activity by 3.2-fold (P < 0.05 vs control). Methylene blue (1 microM), an inhibitor of both NO synthase and guanylate cyclase activities, completely abolished this effect. Cells previously exposed to SNAP and SIN-1 exhibited a significant protection against the cytotoxicity mediated by hydrogen peroxide (250 microM) (P < 0.05). Conversely, SNP did not show any protective effects, possibly because of catalytic iron released during its chemical decomposition. In fact, the iron chelator deferoxamine (5 mM) completely suppressed the SNP-mediated cytotoxicity and partially attenuated the activity of heme oxygenase to a level equal to that mediated by SIN-1 and SNAP. These results indicate that NO is a determinant in the modulation of the activity of heme oxygenase leading to a major resistance of the endothelium to oxidative stress.

Animals↗
PubMed1998

Cytoprotective effect of trimetazidine on 75 min warm renal ischemia-reperfusion injury in rats.

In this experimental study, we evaluated the effect of trimetazidine (TMZ) on renal ischemia-reperfusion (IR) injury in Sprague-Dawley rats. Renal IR was achieved by a 75-min clamping of the left renal pedicle and subsequent 24 h reperfusion, after right nephrectomy was performed. The rats were randomly divided into three groups: group 1 (sham-operated: no IR injury), group 2 (ischemic control: saline treatment), and group 3 (3 mg/kg TMZ before ischemia). After 24 h of reperfusion, blood samples and renal tissue samples were taken to measure the levels of creatinine, tissue malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) activity. Histopathological changes were evaluated. In addition, the 7-day survival rates in each group were evaluated. We found significant increases in the levels of creatinine and tissue MDA, severe acute tubular necrosis, and a significant decrease in the activity of the GSH-Px in group 2. There were significant decreases in the levels of creatinine and tissue MDA, mild acute tubular necrosis, and a significant increase in activity of the GSH-Px in group 3 when compared with the control group (p <0.05). Statistically significant differences (p <0.05) in survival were noted between the ischemic control and sham-operated and TMZ groups. We have concluded that TMZ is able to protect the kidney from warm IR injury.

Animals↗
PubMed2002

Activation of the metallothionein IIA promoter and other key stress response elements by ursodeoxycholate in HepG2 cells: relevance to the cytoprotective function of ursodeoxycholate.

Ursodeoxycholate, used to treat a variety of pathologies, has the ability to reverse cytotoxic and hepatotoxic conditions. We examined HepG2, a hepatic cell line, treated with increasing levels of ursodeoxycholate, for responses of a range of promoters/response elements responsive to DNA damage, heavy metal ions, protein denaturants, aromatic hydrocarbons, retinoids, changes in intracellular AMP levels, end endoplasmic reticulum stress. The metallothionein IIA promoter was the most highly activated by ursodeoxycholate. Since ursodeoxycholate protects against the cytotoxic effects of deoxycholate, our data, combined with observations made by others, implicate metallothionein IIA as being important in this protective pathway.

Cell Survival↗
PubMedDate not supplied

Nuclear hormone and orphan receptors: their role in neuronal differentiation and cytoprotection and in the pathogenesis of Parkinson's disease.

Human nuclear hormone receptors (NHR) and orphan receptors (NOR) act as transcription factors in response to a wide range of circulating hormones and unknown ligands. A role for NHR and NOR in disorders of the subcortical dopaminergic pathways such as Parkinson's disease (PD) is suggested by a wealth of recent data including experimental observations. Both classes of receptors promote the formation of specific neuronal identities, tissue patterning during embryonic development and the maturation of vulnerable monoaminergic and cholinergic neurons. NHR and NOR are also known to exert a neuroprotective function on adult neurons. The scope of this review is to revisit the functional profile of these receptors with particular reference to their activity in the development of selected neuronal populations relevant to the pathophysiology of PD and to discuss how they may relate to the neuropathological and clinical expression of the disease.

Animals↗
PubMed1992

Cytoprotective action of beraprost sodium against peroxide-induced damage in vascular endothelial cells.

Using a peroxide-injured endothelial cell model, beraprost sodium (beraprost) was tested in relation to the action to protect against the damage of vascular endothelial cells employing the viability of the cells and change in lipid peroxides as the indicators. At a concentration of 1-3 mumol/l or higher, beraprost significantly inhibited the decrease in viability of the cells and the increase in lipid peroxides level caused by t-butyl hydroperoxide or 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. When similar tests were conducted with prostaglandin I2, its inhibiting action was equal to or slightly weaker than that of beraprost unlike PGE1 and PGD2. This action of beraprost in inhibiting cell damage caused by peroxides suggests that beraprost may be useful for protecting cells from damage due to ischemic diseases.

Animals↗
PubMedDate not supplied

Cytoprotection with misoprostol: use in the treatment and prevention of ulcers.

Prostaglandins protect the gastric mucosa by decreasing gastric acid secretion, increasing mucus and bicarbonate production and maintaining mucosal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastroduodenal damage and this is due, at least in part, to inhibition of mucosal prostaglandin production. Misoprostol is a synthetic analogue of prostaglandin E1 which has been used in the healing of ulcers and prevention of peptic ulcers in patients taking NSAIDs. Misoprostol is of equal efficacy to H2 antagonists in the healing of ordinary peptic ulcers (not associated with NSAIDs). Misoprostol is superior to placebo in healing NSAID ulcers during continued NSAID treatment but there have been no comparative trials with other ulcer-healing drugs. Misoprostol, H2 antagonists and sucralfate are of similar efficacy in prevention of NSAID-associated duodenal ulcers but misoprostol is more effective in prevention of gastric ulcers. Misoprostol has not been compared to omeprazole in this situation.

Animals↗
PubMed1984

Aspirin-induced damage in the dog Heidenhain pouch and cytoprotection with 16,16-dimethyl PGE2.

The gastric mucosa of animals and man can be damaged by noxious agents and protected by prostaglandins. We developed a Heidenhain pouch dog model which allows the study of multiple doses of the protective or noxious agent. Mucosal damage in the pouch caused by instillation of 160 mM aspirin suspended in 150 mM HCl for two 15-min periods was determined by measuring hemoglobin concentration in isotonic mannitol washes. Hemoglobin levels 24 h after the administration of the acid-aspirin suspension were significantly higher than basal levels. Pretreatment with oral doses of 0.3-3 micrograms/kg 16,16-dimethyl PGE2 at 24 and 18 h and 30 min before the acid-aspirin suspension decreased hemoglobin concentrations in the washes (p less than 0.001).

16,16-Dimethylprostaglandin E2↗
PubMed1988

Gastric cytoprotection by tetraprenylacetone in human subjects.

We assessed the inhibition by tetraprenylacetone (TPA) of gastric mucosal damage caused by ethanol in human subjects. Seventeen healthy volunteers were given either TPA (a 50-mg capsule) or a placebo 3 times daily for 5 days. Then, 20 ml of 70% ethanol were sprayed onto the gastric antrum and 15 min later, visible mucosal lesions were evaluated with an endoscope, and biopsy specimens were taken from mucosa that looked normal but had been sprayed with ethanol. The specimens were observed by light microscopy and scanning electron microscopy. The gross mucosal damage was significantly less (p less than 0.05) in the subjects given TPA than in those given the placebo. Hyperemia and hemorrhage in the mucosa and surface epithelial damage were also significantly less (p less than 0.05) in the subjects given TPA. The results suggested that TPA protects the gastric mucosa from damage by ethanol as judged not only by the gross appearance of the mucosa but also by microscopic observation.

Adult↗
PubMed1988

Changes of rat gastric mucus glycoproteins in cytoprotection: influences of prostaglandin derivatives.

The effects of two synthetic prostaglandin E derivatives on mucus glycoproteins in the stomachs of rats were evaluated. Neither derivative caused change in mucus glycoprotein content in the gastric corpus or antrum, but both increased the biosynthetic activity of mucus glycoproteins in these regions (about 15-30%). Furthermore, the effects of the pretreatment of these derivatives on conserving mucus glycoproteins in ethanol-induced gastric lesions were examined. Treatment with these derivatives 60 min prior to 70% ethanol administration markedly inhibits the decrease in gastric mucus glycoprotein content caused by 70% ethanol. But the glycoprotein content under these pretreatment conditions was significantly less (12-19%) than that in the control group without any drug treatment.

Alprostadil↗
PubMed1991

Role of gastric mucosal blood flow in cytoprotection.

We compared the effects of graded doses of misoprostol (50-200 mg), omeprazole (12.5-50 mg), cimetidine (6.25-50 mg) and sucralfate (50-200 mg) on gastric mucosal blood flow as measured by laser Doppler flowmetry and gastric mucosal injury induced by ethanol. The results demonstrated that sucralfate, misoprostol and omeprazole, but not cimetidine, increased gastric mucosal blood flow in a dose-dependent manner and protected the mucosa against ethanol damage. The peak and summation blood flow were significantly greater with sucralfate than with misoprostol and omeprazole, but the degree of mucosal protection was similar. These results indicate that the increase in gastric mucosal blood flow, an action which is common to the three drugs, plays an important role in gastric mucosal protection, but other factors are also involved.

Alprostadil↗
PubMed2000

Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury.

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lung transplantation. We investigated whether a nitric oxide donor, nitroglycerin (NTG), could suppress the oxidative stress of IR injury and improve pulmonary function after reperfusion in an ex vivo rat lung perfusion model. In Fresh group of animals, the lungs were flushed with perfusate, followed immediately by reperfusion, and no lung injury was observed. In NTG- and NTG+ groups of animals, the lungs were flushed with perfusate alone or perfusate containing NTG, respectively. Harvested lung and heart blocks from these latter two groups were immersed in the corresponding perfusate at 4 degrees C for 15 h, and were then reperfused for 60 min. Reperfusion induced pulmonary edema in the NTG- group, but not in the NTG+ group. Shunt fractions in NTG+ group were significantly lower than in the NTG- group throughout reperfusion. NTG had no effect on pulmonary arterial pressure or myeloperoxidase activity. In contrast, oxidative DNA damage assessed immunohistochemically with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epithelium > pulmonary endothelium > bronchial epithelium. NTG treatment significantly decreased staining with the anti-8-OHdG antibody in all three areas of tissue. Therefore, administration of NTG attenuates the oxidative stress of IR injury, and may improve pulmonary function after reperfusion.

Animals↗
PubMed1987

Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules.

Roles for both the tripeptide, GSH, and individual amino acids in modifying the cellular response to oxygen deprivation-induced injury have been suggested by prior work in kidney and other tissues, but the precise interrelationships have not been clearly defined. We have studied the effects of GSH, its component amino acids, and related compounds on the behavior of isolated renal proximal tubules in a well characterized model of hypoxic injury in vitro. GSH, the combination of cysteine, glutamate, and glycine and glycine alone, when present in the medium during 30 min hypoxia, a duration sufficient to produce extensive irreversible injury in untreated tubules, were protective. Significant effects were detected at 0.25 mM concentrations of the reagents, and protection was nearly complete at concentrations of 1 mM and above. Glutamate and cysteine alone were not protective. The exogenous GSH added to the tubule suspensions was rapidly degraded to its component amino acids. Treatment of tubules with GSH or cysteine, but not glycine, increased intracellular GSH levels. Oxidized GSH was protective. Serine, N-(2-mercaptopropionyl)-glycine, and a panel of agents known to modify injury produced by reactive oxygen metabolites were without benefit. These observations identify a novel and potent action of glycine to modify the course of hypoxic renal tubular cell injury. This effect is independent of changes in cellular GSH metabolism and appears to be unrelated to alterations of cell thiols or reactive oxygen metabolites. Further elucidation of its mechanism may provide insight into both the basic pathophysiology of oxygen deprivation-induced cell injury and a practical way to ameliorate it.

Adenosine Triphosphate↗