Biomedical subjects

K J Ivey

Publications and source records attributed to K J Ivey.

At least 19 recordsLinked to original sources

PubMed1999

Role of antioxidant defenses against ethanol-induced damage in cultured rat gastric epithelial cells.

Reactive oxygen species appears to be involved in the pathogenesis of ethanol-induced gastric mucosal injury in vivo. Because ingested ethanol diffuses into the gastric mucosa, targeting both epithelium and endothelium, in the present study we examined the possible protective effect of antioxidants on ethanol damage in gastric epithelial cells and endothelial cells in vitro. Cytotoxicity by ethanol was quantified by measuring 51Cr release. The effects of impairment of the glutathione redox cycle and of inhibition of cellular catalase were examined. The generation of superoxide was assessed by the reduction in cytochrome c. Ethanol caused a time- and dose-dependent increase in 51Cr release from epithelial cells. Incubation of cells with DL-buthionine-(S,R)-sulfoximine, while reducing glutathione production, dose dependently enhanced ethanol-induced injury. 1,3-Bis(chloroethyl)-nitrosourea, while inhibiting glutathione reductase activity, also sensitized cells to ethanol. In contrast, the inhibition of catalase with 3-amino-1,2, 4-triazole did not alter the susceptibility of epithelial cells to ethanol. Ethanol induced damage to endothelial cells in a similar fashion. In endothelial cells, however, neither impairment of the glutathione cycle nor inhibition of catalase influenced ethanol-induced damage. Epithelial cells, when exposed to ethanol, increased superoxide production as a function of ethanol concentration, whereas endothelial cells did not. The glutathione redox cycle, but not cellular catalase, plays a critical role in protecting epithelial cells against ethanol damage, whereas neither antioxidant seems to play a role in protection of endothelial cells. The distinct difference in antioxidant protection against ethanol appears to depend on the capability of each cell to produce cytotoxic oxygen species in response to ethanol exposure.

Amitrole↗

PubMed1997

Antioxidant defenses of cultured colonic epithelial cells against reactive oxygen metabolites.

Reactive oxygen metabolites produce colonic epithelial cellular injury. The present study evaluated the protective role of cellular superoxide dismutase, catalase, and glutathione (GSH) redox cycle in cultured rabbit colonic cells. Cultured rabbit colonic epithelial cells were exposed to reactive oxygen metabolites generated by hypoxanthine (1 mM) and xanthine oxidase (1 mU/ml) for up to 5 h. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Pretreatment with diethyldithiocarbamate (inhibitor of superoxide dismutase) reduced activity of cellular superoxide dismutase and increased 51Cr release caused by hypoxanthine/xanthine oxidase from colonic cells. Pretreatment with diethyl maleate (covalently binds GSH as catalyzed by GSH transferase), or buthionine sulfoximine (inhibitor of gamma-glutamylcysteine synthetase) decreased cellular GSH and enhanced reactive oxygen metabolites induced injury. Pretreatment with bis(chloroethyl)-nitrosourea (inhibitor of GSH reductase) inhibited activity of GSH reductase and increased 51Cr release from colonic cells. Preincubation with aminotriazole (inhibitor of catalase) reduced cellular catalase, but did not affect cellular injury. Therefore, we concluded that both cellular superoxide dismutase and the GSH redox cycle appeared to play a role in detoxifying reactive oxygen metabolites and that cellular catalase may be less important in rabbit colonic epithelial cells.

Animals↗

PubMed1997

Hydrogen peroxide-mediated cytotoxicity to cultured colonic epithelial cells.

Reactive oxygen metabolites (ROM) contribute to colonic cellular injury, in certain pathophysiological conditions. We investigated the role of iron and individual metabolites in their cytotoxicity to cultured colonic epithelial cells from adult white rabbits. Reactive oxygen metabolites, enzymatically generated by hypoxanthine/xanthine oxidase, have a direct cytotoxic effect on cultured colonic epithelial cells. This cellular injury was inhibited by catalase but not SOD. Damage was not aggravated by ferrous iron or EDTA-chelated iron. Such damage was prevented by chelating intracellular iron, but not extracellular iron. These results suggest that H2O2 is more toxic to colonic epithelial cells than 02.- and OH. in the extracellular space. H2O2 enter the intracellular space and is converted to the more reactive and harmful OH. leading to cellular injury in the presence of intracellular iron.

Animals↗

PubMed1996

Nitric oxide enhances cytotoxicity of cultured rabbit gastric mucosal cells induced by hydrogen peroxide.

While NO has been reported to act as a protective factor to gastric mucosa, it has been shown to be cytotoxic to various cells. NO also has been demonstrated to stimulate prostaglandin (PG) release and mucous glycoprotein secretion which could result in the activation of gastric defensive mechanisms. We examined the effect of NO on cytotoxicity induced by hydrogen peroxide, and mucous glycoprotein secretion and PGE2 release from cultured rabbit gastric mucosal cells. NO enhanced cytotoxicity induced by hydrogen peroxide. Defensive prostaglandin E2 release and mucous glycoprotein secretion were not altered by NO. Under certain circumstances, NO might behave as an aggressive factor in gastric mucosal injury.

Animals↗

PubMed1996

Significance of ammonia in the genesis of gastric epithelial lesions induced by Helicobacter pylori: an in vitro study with different bacterial strains and urea concentrations.

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain. The effect of VacA and ammonia was evaluated with and without addition of 10 mM urea, a physiological concentration for the human stomach, and with and without addition of 0.5 mg/ml acetohydroxamic and (AHA), an urease inhibitor. Our data show that: (1) both urease-positive H. pylori strains caused cell vacuolation in the absence of urea, the VacA-positive strain being approximatively twice as potent as the VacA-negative strain; (2) addition of urea to the culture medium caused an approximatively 3-fold increase in the vacuolating activity of both urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert any vacuolating effect, either in the presence or in the absence of urea; (4) the ratio between cell vacuolation induced by VacA-positive and VacA-negative strains was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and about 6 in the presence of AHA, either with or without urea added. The increment of vacuolation is likely due to an interaction between AHA and VacA. In conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when physiological levels of urea are present in the incubation medium. This finding suggests that all urease-positive H. pylori strains, both with and without VacA expression, should be considered as potentially cytotoxic for the human gastric mucosa, although VacA enhances the severity of cell damage.

Ammonia↗

PubMed1995

Adaptive cytoprotection in cultured rat gastric mucus-producing cells. Role of mucus and prostaglandin synthesis.

In cultured gastric mucosal cells, we investigated whether: (1) adaptive cytoprotection was associated with stimulation of endogenous prostaglandin synthesis; (2) prostaglandins given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage; and (3) a relationship existed between cytoprotection and mucus release. Cytolysis was quantified by measuring 51Cr release from prelabeled cells. Mucus release was determined by measurement of [3H]glucosamine release. Concentrations of ethanol > 12% caused cell damage and increased 51Cr release dose dependently. Pretreatment with low concentrations of ethanol (0.5-1.5%) decreased ethanol-induced 51Cr release, but also decreased prostaglandin E2 synthesis. Prostaglandin E2 and 16,16-dimethyl prostaglandin E2 given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage. Treatment with low concentrations of ethanol (1.5%) increased mucus release from cultured gastric mucosal cells. However, prostaglandin E2 and 16,16-dimethyl prostaglandin E2 did not affect mucus release. We conclude that in cultured gastric mucus-producing cells: (1) adaptive cytoprotection occurs without stimulation of endogenous prostaglandin synthesis but with increase in mucus release; and (2) exogenous prostaglandins are cytoprotective against ethanol-induced gastric mucosal cell damage without stimulating mucus release in vitro. We postulate that adaptive cytoprotection in cultured gastric mucus-producing cells is not mediated by prostaglandin, but by mucus released in response to a mild irritant.

16,16-Dimethylprostaglandin E2↗

PubMed1995

Relationships between metal ions and oxygen free radicals in ethanol-induced damage to cultured rat gastric mucosal cells.

The current study investigated whether metal ions were cytoprotective against ethanol-induced injury to cultured rat gastric mucosal cells in vitro. Secondly, the relationships between oxygen free radicals and cytoprotection by metal ions were examined. Cultured cells exposed to ethanol produced superoxide anion, as assessed by reduction of cytochrome c, in a time-related fashion, and the production of superoxide anion increased dose-dependently as the concentration of ethanol increased. Cellular damage increased proportionately to the production of superoxide anion. ZnCl2, AlCl3, CoCl2, CuCl2, and CdCl2 significantly diminished ethanol-induced injury dose-dependently. All of the agents studied decreased the reduction of cytochrome c in ethanol-induced damage dose-dependently. These results led to the conclusions that: (1) cultured rat gastric mucosal cells exposed to ethanol generate oxygen free radicals; (2) the production of oxygen free radicals is closely linked with ethanol-induced damage to the cells; and (3) metal ions decrease ethanol-induced gastric mucosal cell damage in vitro. Metal ions protect cultured rat gastric mucosal cells from ethanol-induced damage in which oxygen free radicals participate.

Aluminum Chloride↗

PubMed1994

Reactive oxygen metabolite-induced toxicity to cultured bovine endothelial cells: status of cellular iron in mediating injury.

We aimed to determine the status of iron in mediating oxidant-induced damage to cultured bovine aortic endothelial cells. Chromium-51-labeled cells were exposed to reaction mixtures of xanthine oxidase/hypoxanthine and glucose oxidase/glucose; these produce superoxide and hydrogen peroxide, or hydrogen peroxide, respectively. Xanthine oxidase caused a dose dependent increase of 51Cr release. Damage was prevented by allopurinol, oxypurinol, and extracellular catalase, but not by superoxide dismutase. Prevention of xanthine oxidase-induced damage by catalase was blocked by an inhibitor of catalase, aminotriazole. Glucose oxidase also caused a dose-dependent increase of 51Ci release. Glucose oxidase-induced injury, which was catalase-inhibitable, was not prevented by extracellular superoxide dismutase. Both addition of and pretreatment with deferoxamine (a chelator of Fe3+) prevented glucose oxidase-induced injury. The presence of phenanthroline (a chelator of divalent Fe2+) prevented glucose oxidase-induced 51Cr release, whereas pretreatment with the agent did not. Apotransferrin (a membrane impermeable iron binding protein) failed to influence damage. Neither deferoxamine nor phenanthroline influenced cellular antioxidant defenses, or inhibited lysis by non-oxidant toxic agents. Treatment with allopurinol and oxypurinol, which inhibited cellular xanthine oxidase, failed to prevent glucose oxidase injury. We conclude that (1) among the oxygen species extracellularly generated by xanthine oxidase/hypoxanthine, hydrogen peroxide induces damage via a reaction on cellular iron; (2) deferoxamine and phenanthroline protect cells by chelating Fe3+ and Fe2+, respectively; and (3) reduction of cellular stored iron (Fe3+) to Fe2+ may be prerequisite for mediation of oxidant-induced injury, but this occurs independently of extracellular superoxide or cellular xanthine oxidase-derived superoxide.

Allopurinol↗

PubMed1994

Role of iron and glutathione redox cycle in acetaminophen-induced cytotoxicity to cultured rat hepatocytes.

The aims of this study were to investigate the roles of iron as a catalyst in reactive oxygen metabolite-mediated cellular injury and of the endogenous antioxidant defenses against acetaminophen-induced cytotoxicity in cultured rat hepatocytes. Hepatocytes were isolated and cultured from either 3-methylcholanthrene-treated or untreated rats. Cytotoxicity was evaluated by measuring 51Cr and lactate dehydrogenase release. Acetaminophen caused dose-dependent cytotoxicity in 3-methylcholanthrene-treated, but not untreated, cells. There was a good correlation between 51Cr and lactate dehydrogenase release values. Pretreatment with both diethyl maleate, which covalently binds glutathione as catalyzed by glutathione-S-transferase, and bis(chloroethyl)-nitrosourea, an inhibitor of glutathione reductase, enhanced acetaminophen-induced cytotoxicity. Inhibition of endogenous catalase activity by pretreatment with aminotriazole did not affect acetaminophen-induced cellular damage. Addition of exogenous catalase failed to protect against acetaminophen-induced cytotoxicity. Preincubation with both deferoxamine, a ferric iron chelator, and phenanthroline, a ferrous iron chelator, diminished acetaminophen-induced cytotoxicity. These results indicate that iron is crucial in mediating acetaminophen-induced cytotoxicity and that the glutathione redox cycle, but not catalase, plays a critical role in the endogenous defenses against acetaminophen-induced cellular damage in cultured rat hepatocytes in vitro.

Acetaminophen↗

PubMed1994

Protection of cultured rat gastric cells against oxidant-induced damage by exogenous glutathione.

BACKGROUND/AIMS: Reduced glutathione (GSH) is an intracellular protectant against oxidants. The present study determined whether extracellular GSH protects against oxidant damage or whether an uptake system of GSH is present in cultured gastric cells. METHODS: Hydrogen peroxide was generated by glucose oxidase and glucose. Cytotoxicity was assessed by 51Cr release. Intracellular GSH was assayed by the method of Tietze. RESULTS: Pretreatment with extracellular GSH decreased H2O2-induced 51Cr release. Treatment with GSH enhanced cellular GSH content. Protection by pretreatment with GSH was prevented by buthionine sulfoximine (an inhibitor of gamma-glutamylcysteine synthetase). Enhancement of intracellular GSH was also prevented by buthionine sulfoximine. Acivicin (an inhibitor of gamma-glutamyl transpeptidase) prevented intracellular accumulation of GSH from extracellular GSH. Cysteine was effective in preventing damage and enhancing intracellular GSH content, whereas both glutamine and glycine were not. CONCLUSIONS: Extracellular GSH protects cultured gastric cells from H2O2 damage by accelerating intracellular GSH synthesis; this is mediated by membrane-bound gamma-glutamyl transpeptidase acting on extracellular GSH (which supplies these cells with cysteine) and then by intracellular gamma-glutamylcysteine synthetase.

Animals↗

PubMed1994

Stimulation of prostaglandin E2 release from cultured rabbit gastric cells by sodium deoxycholate.

Although bile salts are irritants in the gastric mucosa, their effects on prostaglandin (PG) release have not been well studied. We investigated the effects of bile salts on PGE2 release and the possible mechanisms involved. Cultured rabbit gastric mucous epithelial cells were studied. PGE2 was measured by radioimmunoassay. Intracellular free Ca2+ concentration was measured with Ca2+ fluorescent dye indo-1 AM. Dihydroxy bile salts, such as chenodeoxycholate and deoxycholate (DC), dose-dependently increased PGE2 release, while non-dihydroxy bile salts did not. Since agents involved in the cellular signal transduction system have been reported to play important roles in PG release, the possible involvement of Ca2+, calmodulin, and protein kinase C (PKC) in DC-induced PGE2 release was studied. Deprivation of Ca2+ from the medium blocked DC-induced PGE2 release. Lanthanum (La3+), which displaced surface-bound Ca2+, suppressed DC-induced PGE2. However, BAPTA (a chelator of intracellular Ca2+) did not decrease it. Neither calmodulin inhibitors nor PKC inhibitors altered DC-induced PGE2 release. DC increased intracellular free Ca2+ concentrations. This effect was blocked by deprivation of Ca2+ from the medium. Quinacrine (a phospholipase A2 inhibitor) blocked DC-induced PGE2 release. These results suggest that in cultured rabbit gastric cells, deoxycholate stimulates PGE2 release mainly through the influx of extracellular Ca2+.

Animals↗

PubMed1994

The therapeutic strategy for peptic ulcer disease.

Therapy of acid/peptic disease has evolved since the 1970s with development of: (i) more accurate endoscopes which permit precise examination and documentation of upper gastrointestinal lesions; and (ii) the histamine H2-receptor antagonists. As well, refined standards for clinical investigation have contributed to the clinical study of acid/peptide diseases. Initially, ulcer diseases were considered to be principally secondary to increased 'aggressive' factors (acid, pepsin) and the therapeutic focus was directed at antacids, the progressive evolution of additional histamine H2-receptor antagonists and recently the H+/K(+)-ATPase inhibitors. Later studies indicated efficacy of sucralfate, low dose antacids and prostaglandin analogues, drugs with either no or only modest antisecretory effect. This led to studies on the role of gastroduodenal mucosal defensive factors (mucus and bicarbonate secretion, blood flow, leucocyte adherence, cytokines, reactive oxygen radicals). The prominent role played by aspirin and other non-steroidal anti-inflammatory drugs (NSAID) in initiating and causing recurrence of peptic ulcer disease has been increasingly realized. Recognition of those most at risk for NSAID-induced complication has led to newer approaches to treatment and prevention. Since 1983, Helicobacter pylori has been incriminated as a major factor in the pathogenesis of ulcer disease, particularly ulcer recurrences. Treatment of such ulcers now includes antibiotics and bismuth compounds in order to eradicate H. pylori. This therapeutic regimen is in a state of flux ('triple therapy' vs a H+/K(+)-ATPase inhibitor plus antibiotic) as is the question of how to work up and treat patients initially presenting with ulcer symptoms.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1994

Protective role of intracellular superoxide dismutase against extracellular oxidants in cultured rat gastric cells.

We examined the role of intracellular superoxide dismutase (SOD) as an antioxidant by studying the effect of diethyldithiocarbamate (DDC) on extracellular H2O2-induced damage in cultured rat gastric mucosal cells. 51Cr-labeled monolayers from rat stomachs were exposed to glucose oxidase-generated H2O2 or reagent H2O2, which both caused a dose-dependent increase in 51Cr release. DDC dose-dependently enhanced 51Cr release by hydrogen peroxide, corresponding with inhibition of endogenous SOD activity. This inhibition was not associated either with modulation of other antioxidant defenses, or with potentiation of injury by nonoxidant toxic agents. Enhanced hydrogen peroxide damage by DDC was significantly prevented by chelating cellular iron with deferoxamine or phenanthroline. Inhibition of cellular xanthine oxidase (possible source of superoxide production) by oxypurinol neither prevented lysis by hydrogen peroxide nor diminished DDC-induced sensitization to H2O2. We conclude that (a) extracellular H2O2 induces dose dependent damage to cultured gastric mucosal cells; (b) intracellular SOD plays an important role in preventing H2O2 damage; (c) generation of superoxide seems to occur intracellularly after exposure to H2O2, but independent of cellular xanthine oxidase; and (d) cellular iron mediates the damage by catalyzing the production of more reactive species from superoxide and H2O2, the process which causes ultimate cell injury.

Animals↗

PubMed1994

Bile salts stimulate mucous glycoprotein secretion from cultured rabbit gastric mucosal cells.

Resistance of gastric mucosa to damage is increased after exposure to mild irritants such as bile salts (adaptive cytoprotection). Mucus secretion also contributes to gastric cytoprotection. We investigated whether bile salts stimulate mucous glycoprotein secretion from cultured rabbit gastric mucosal cells. Because prostaglandins (PGs) stimulate mucus secretion, we assessed the role of endogenous PG release in bile salt-stimulated mucus secretion. Because Ca2+ plays a role in PGE2 release, the role of extracellular Ca2+ on PGE2 release and mucus secretion by bile salts was also studied. Rabbit gastric mucosal cells were prepared with collagenase and ethyl-enediaminetetraacetic acid. These cells were cultured as described previously. Cytotoxicity of bile salts was quantified by measuring chromium 51 release from prelabeled cells. PGE2 was measured by radioimmunoassay. Mucous glycoprotein secretion was assessed by tritiated glucosamine release assay. Deoxycholate (DC) and glycodeoxycholate (GDC) stimulated tritiated glucosamine release in doses that were not cytotoxic to the cultured cells. DC stimulated PGE2 release that was blocked by deprivation of extracellular Ca2+. GDC did not stimulate PGE2 release. Neither DC-stimulated nor GDC-stimulated mucus secretion was affected by indomethacin. Deprivation of extracellular Ca2+ did not affect DC-stimulated or GDC-stimulated mucus secretion. Bile salts stimulated mucous glycoprotein secretion from cultured rabbit gastric mucosal cells. This effect occurred independently of changes in endogenous PGE2 or extracellular Ca2+ concentrations.

Animals↗

PubMed1993

Na+,K(+)-ATPase of gastric cells. A target of Helicobacter pylori cytotoxic activity.

The present study shows a direct impairing action of a cytotoxin-producing Helicobacter pylori strain on the Na+,K(+)-ATPase (evaluated as K(+)-dependent phosphatase activity) of human gastric epithelial cells in culture. The toxin itself is likely involved in this action which may also account for the cell edema found in vivo in Helicobacter pylori-colonized stomach.

Adenocarcinoma↗

PubMed1993

Antioxidant protection against oxidant-induced damage in cultured gastric mucosal cells.

Gastric epithelium is exposed not only to oxidants generated within the lumen, but also to those produced by ischemia/reperfusion. This study examined the mechanism(s) of oxidant-induced injury to cultured rat gastric mucosal cells, and characterized the antioxidant profile of these cells. Hydrogen peroxide (H2O2), generated by glucose oxidase, damaged cells dose-dependently, as assessed by increased leakage of labeled 51Cr. Glucose oxidase-induced damage was prevented by exogenous catalase (but not by exogenous superoxide dismutase). Chelation of cellular iron with desferrioxamine or phenanthroline specifically protected cells against H2O2, whereas binding of extracellular iron with apotransferrin failed to. Disruption of the glutathione redox cycle at three independent sites rendered cells less resistant to H2O2, whereas inhibition of cellular catalase did not result in sensitization of cells to H2O2. In conclusion, (1) oxidant injury induced by extracellular H2O2 is mediated by intracellular iron; (2) extracellular superoxide is not involved in the damaging process; and (3) the glutathione redox cycle plays a principal role in detoxifying H2O2 as a cellular antioxidant in cultured gastric mucosal cells.

Animals↗

PubMed1993

Role of iron and superoxide in mediating hydrogen peroxide injury to cultured rat gastric cells.

BACKGROUND: Gastric epithelium is exposed to toxic, reactive oxygen species generated within the lumen. The present study examined the role of cellular iron and superoxide (O2-) in mediating hydrogen peroxide (H2O2)-induced damage to cultured gastric mucosal cells. METHODS: H2O2 was generated by glucose oxidase acting on b-D(+)glucose. Cytotoxicity was assessed by 51Cr release from prelabeled cells. RESULTS: Deferoxamine (a chelator of Fe3+) prevented injury induced by H2O2, whether present before or during H2O2 production. In contrast, whereas the presence of phenanthroline (a chelator of Fe2+) during the cytotoxicity assay prevented damage, prior treatment with the agent did not; this suggested that cellular Fe3+ reduced to Fe2+ upon exposure to H2O2 is responsible for damage. Neither extracellular superoxide dismutase nor inhibitors of xanthine oxidase (a possible source of cellular O2- production) protected against H2O2. Further, protection by iron chelators was not associated with modulation of endogenous antioxidants. CONCLUSIONS: Deferoxamine and phenanthroline protect cells from H2O2 by chelating stored iron (Fe3+) or reduced iron (Fe2+), respectively. Reduction of cellular Fe3+ appears to be a prerequisite for mediation of damage, but this reduction is independent of extracellular O2- or cellular xanthine oxidase-derived O2-.

Allopurinol↗

PubMed1993

Role for mucous glycoprotein in protecting cultured rat gastric mucosal cells against toxic oxygen metabolites.

The gastric epithelium is exposed to oxygen radicals that are generated within the lumen. Much interest has been focused on the role of mucus in maintaining integrity of the gastric mucosa against oxidants, because gastric mucus may act as a scavenger of oxygen radicals. The aim of this study was to assess the role of mucous glycoprotein in protecting cultured gastric epithelial cells against oxygen radicals. Monolayer cultures of rat gastric mucus-producing cells were studied. Oxygen radicals were generated by hypoxanthine and xanthine oxidase. Cytotoxicity was quantified by measuring chromium 51 release form prelabeled cells. Rate of mucous synthesis was estimated by incorporation of tritiated glucosamine into the cells. The effects of tetraprenyl acetone (a stimulant of mucus production) and N-acetyl-L-cysteine (a mucolytic agent) on oxygen radical-induced damage were determined. Preincubation with tetrapenyl acetone, while stimulating mucous glycoprotein by the cultured cells, caused a dose-dependent reduction of hypoxanthine-xanthine oxidase-induced 51Cr release, reaching maximum protection of the damage by 31% to 50%. In contrast, pretreatment with N-acetyl-L-cysteine potentiated oxygen radical-induced 51Cr release dose dependently. The protective effect of tetraprenyl acetone was significantly abolished by N-acetyl-L-cysteine. Neither tetraprenyl acetone nor N-acetyl-L-cysteine alone under the conditions of this study affected the cellular content of glutathione, which modulates oxygen radical injury to these cells. These results suggest that mucous glycoprotein partially but significantly protects cultured gastric epithelial cells against extracellularly generated oxygen radicals. It seems likely, therefore, that gastric mucus is involved in antioxidant defenses in these cells.

Acetylcysteine↗