Cytoprotective effect of acetaminophen against taurocholate-induced damage to rat gastric monolayer cultures

Ota, Shinichi; Razandi, Mahnaz; Sekhon, Sant S.; Terano, Akira; Hiraishi, Hideyuki; Ivey, Kevin J.

doi:10.1007/bf01535988

Cited by 17 publications

(3 citation statements)

References 29 publications

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“…Sev eral mechanisms have been proposed for the protection of gastric mucosa by acetamino phen. For example, in gastric lesions induced by the water immersion restraint stress meth od, acetaminophen was thought to protect the gastric mucosa by inhibiting the reduction in gastric PGE2 levels [4,24] or to stimulate PGEi synthesis in the gastric mucosa [25], However, in some studies, acetaminophen failed to increase PGE2 content but enhanced gastric secretion of mucus or directly pro tected the gastric epithelial cells, independent of PG synthesis [3,6,23]. Thus, gastric pro tection by acetaminophen is not attributable to a single mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…In con trast to nonsteroidal anti-inflammatory drugs (NSAIDs), a previous study has shown that acetaminophen does not induce serious gastrointestinal damage in man [1], In addition, administration of a high dose of acetamino phen (orally or intraperitoneally) has been reported to exhibit a protective effect on gas tric mucosa against various irritants, such as NSAIDs, ethanol and stress [2][3][4], It has been stated that acetaminophen may stimulate prostaglandin Ea (PGE2) synthesis to protect gastric mucosa [5], On the contrary, some reports have suggested that protection by acetaminophen was not attributable to the stimulation of PG synthesis but due to an increase in mucus secretion [3] or to a direct effect on gastric mucosal cells [6], Other studies have reported acetamino phen to possess direct antioxidant actions against free-radical-induced oxidative stress in vitro [7][8][9][10], but it remains to be shown if the in vivo gastric protective effect of acet aminophen is due to its antioxidant effect. Superoxide radicals or hydroxyl radicals have been reported to play important roles in the pathogenesis of gastric erosions induced by ischemia-reperfusion in rats [11][12][13][14], There fore, using this model of acute gastric mucosal injury, we studied whether or not the protec tive effect of acetaminophen against ischemia-reperfusion-induced gastric injury is due to antioxidant or radical scavenging ac tions in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Acetaminophen against Acute Gastric Mucosal Lesions Induced by Ischemia-Reperf usion in the Rat

Nakamoto

Kamisaki²,

Wada³

et al. 1997

Pharmacology

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We examined the effect of acetaminophen, an analgesic and antipyretic drug, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Ischemia-reperfusion was induced by clamping the celiac artery for 30 min with a small clip. Sixty minutes after repefusion, the total area of erosions was measured. Acetaminophen (300 and 500 mg/kg) administered intraperitoneally 90 min before the ischemia significantly reduced the total area of erosions. The drug also inhibited the increase in lipid peroxide levels induced by ischemia-reperfusion in the gastric tissue and the increase in lipid peroxidation caused by the hydroxyl radical, OH^·, in vitro. Gastric prostaglandin E₂ (PGE₂) contents tended to increase after ischemia-reperfusion in both control and acetaminophen-treated groups. A significant difference in gastric PGE2 contents between control and acetaminophen-treated groups was not observed. The results indicate that acetaminophen may protect the gastric mucosa against ischemia-reperfusion injury, probably by blocking hydroxyl-radical-induced membrane damage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective Effect of Acetaminophen against Acute Gastric Mucosal Lesions Induced by Ischemia-Reperf usion in the Rat

Nakamoto

Kamisaki²,

Wada³

et al. 1997

Pharmacology

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“…These cells have been derived from rat gastric mucosa. 14,15) Cultured gastric epithelial cells offer a promising tool for evaluating the cytoprotective effects of anti-ulcer agents in the absence of gastric and systemic factors and, thus, may provide a suitable model for studying the mechanisms by which these drugs influence gastrointestinal epithelial cell functions. In our study, primary cultured rat gastric mucosal cells were investigated as an in vitro model to measure the cytoprotective activities of (-)-PAN•Na, (+)-PAN•Na and (±)-PAN•Na.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Pantoprazole Enantiomers on Gastric Mucosal Lesions and Gastric Epithelial Cells in Rats

Chen

Wang

Jia

et al. 2004

JOURNAL OF HEALTH SCIENCE

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(±)-Pantoprazole sodium, [(±)-PAN•Na], is a proton pump inhibitor that is administered as a racemate. The protective effects of (-)-PAN•Na, (+)-PAN•Na and (±)-PAN•Na on various experimental ulcers in animals were compared. (-)-PAN•Na inhibited gastric lesions induced by water-immersion stress, aspirin, ethanol, and reserpine in a dose-dependent manner. The dose that inhibited 50% of lesions (ID 50 ) were 2.72 ± 1.03, 1.60 ± 0.64, 4.12 ± 2.18, and 2.77 ± 0.86 mg/kg, respectively. The ID 50 values of (+)-PAN•Na and (±)-PAN•Na were 1.7, 2.6, 1.8, 2.7 and 1.5, 1.7, 1.6, 1.9 times higher, respectively, than that of (-)-PAN•Na. Primary culture of rat gastric epithelial cells was investigated as an in vitro model for comparing the cell protective effects among the three agents. Exposed to the three drugs at the concentrations of 2.5 × 10 -1 -2.5 × 10 -5 mg/ml, cultured cells were treated with either pH 3.5 medium or 3.5 mM indomethacin. Cytoprotection was evaluated by MTT. (-)-PAN•Na, (+)-PAN•Na and (±)-PAN•Na provided significant cytoprotective effects when the cells were pretreated with the drugs prior to exposure to 3.5 mM indomethacin, whereas, when they were treated concurrently, no significant cytoprotective effects were found. In pH 3.5 medium-induced damage, the three drugs had marked protective effects on gastric cells, however, when the concentration of drugs was high (0.25 mg/ml), only (+)-PAN•Na had significant cytoprotection. We concluded that the cytoprotective mechanisms of (-)-PAN•Na and (+)-PAN•Na are different. The results of in vitro experiments were not in complete accordance with the in vivo results, suggesting that the effects of the three drugs on ulcer inhibition are mainly due to the effects of acid inhibition rather than cytoprotection.

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Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury

Hashimoto

et al. 1991

Hepatology

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Trolox, a hydrophilic analog of vitamin E, was reported to scavenge peroxyl radicals from artificial systems better than its parent compound. Here we examined the possible cytoprotective effect of Trolox in cultured hepatocytes and in the rat liver. In cultured rat hepatocytes, 0.5 to 16 mmol/L Trolox (with optimum between 1 to 2 mmol/L) was observed to prolong the survival of cells exposed to oxyradicals generated with xanthine oxidase-hypoxanthine. The protection by 1 mmol/L Trolox surpassed that provided by either ascorbate, mannitol, superoxide dismutase and/or catalase--each at a level giving its maximal protection in the same system. In both a global and partial model of hepatic ischemia-reperfusion in rats, infusion of Trolox (7.5 to 10 mumol/kg body weight) just before reflow reduced by greater than 80% the liver necrosis sustained in untreated (no Trolox) control rats. Such organ salvage was apparently accompanied by approximately 50% reduction in the amount of hepatic conjugated dienes, which were quantified by a highly specific radiochemical assay. Since conjugated dienes are presumed to be good "markers" of oxyradical damage, our data may have provided a semiquantitative link between free radical-induced necrosis and its chemical imprint in vivo. The data also indicated a relatively rapid and potent antioxidant-like action by Trolox on rat hepatocytes and on the postischemic reperfused rat liver.

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Cytoprotective effect of acetaminophen against taurocholate-induced damage to rat gastric monolayer cultures

Cited by 17 publications

References 29 publications

Protective Effect of Acetaminophen against Acute Gastric Mucosal Lesions Induced by Ischemia-Reperf usion in the Rat

Protective Effect of Acetaminophen against Acute Gastric Mucosal Lesions Induced by Ischemia-Reperf usion in the Rat

Comparison of the Effects of Pantoprazole Enantiomers on Gastric Mucosal Lesions and Gastric Epithelial Cells in Rats

Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury

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