Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man.

Ivey, K.J.; Settree, P

doi:10.1136/gut.17.11.916

Cited by 19 publications

(4 citation statements)

References 16 publications

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“…A wash solution contained 160 mmol/l HCl only. POTENTIAL DIFFERENCE Gastric mucosal potential difference was measured by a previously described technique (Ivey et al, 1975;Andersson and Grossman, 1965;Baskin et al, 1976;Ivey and Settree, 1976) using intravenous and intragastric electrodes filled with a saturated KCl solution in 3 % agar. Continuous recordings were made by means of a strip chart recorder.…”

Section: Test Solutionmentioning

confidence: 99%

Effect of cimetidine on ion fluxes and potential difference across the human stomach

Ivey¹,

Mackercher²

1978

Gut

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SUMMARY The H2-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H+, Na+, K+, and Cl -ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5 05 mEq per 15 minutes controls versus 2-70 cimetidine, P < 0 05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2'01 mEq per 15 minutes versus 0-02, P < 0 05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (P < 0 001). Addition of intragastric acid (pH < 1 -0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion.Changes in acid secretion cannot satisfactorily explain gastric mucosal damage associated with conditions such as gastric ulcer or acute aspirininduced mucosal damage. The ill-defined concept of mucosal resistance has long been used to explain such cases. An attempt to define and measure this resistance objectively was the 'gastric mucosal barrier' concept popularised by Davenport (1970); Ivey (1971); Code et al. (1963);and Reitemeier et al. (1957). Davenport found that topical aspirin induced an increase in the net fluxes of Na+ ions into the gastric lumen and at the same time of H+ ions out. Increased net movement of Na+ ions into the lumen and of H+ ions out was termed 'alteration' or 'damage' to the 'gastric mucosal barrier' which limited potentially damaging H+ ion movement into the gastric mucosa. In Davenport's studies, alteration of net Na+ and H+ fluxes was associated with a fall in PD. Other workers (Chvasta and Cooke, 1972) confirmed this, and so changes in PD became "Address for reprint requests: Kevin J. Ivey,

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Section: Test Solutionmentioning

confidence: 99%

Effect of cimetidine on ion fluxes and potential difference across the human stomach

Ivey¹,

Mackercher²

1978

Gut

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“…6,7 Animal studies have shown evidence of paracetamol-induced intestinal toxicity, and this could be due to mitochondrial injury, generation of reactive oxygen species, depletion of intestinal glutathione, alteration of the gut microbiota, and disruption of intestinal tight junction proteins following exposure to extremely elevated paracetamol concentrations. [8][9][10][11][12] We found in an earlier pilot study that the novel biomarker intestinal fatty acid binding protein (IFABP) was elevated in paracetamol overdose (and several other poisonings). 13 IFABP is a small bowel-specific protein that is present in the cytosol of enterocytes and is released into systemic circulation following injury.…”

Section: Introductionmentioning

confidence: 99%

“…Animal studies have shown evidence of paracetamol‐induced intestinal toxicity, and this could be due to mitochondrial injury, generation of reactive oxygen species, depletion of intestinal glutathione, alteration of the gut microbiota, and disruption of intestinal tight junction proteins following exposure to extremely elevated paracetamol concentrations 8–12 …”

Section: Introductionmentioning

confidence: 99%

Intestinal injury in paracetamol overdose (ATOM‐8)

Perananthan,

Shihana,

Chiew

et al. 2023

J of Gastro and Hepatol

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Background and AimParacetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity.MethodsSerial samples of 30 patients with acute paracetamol overdose (> 10 g or 200 mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut‐related microRNAs (miR‐21, miR‐122, miR‐194, and miR‐215), were analyzed. Sub‐analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2 mmol/L within 12 h post ingestion.ResultsIn paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720 μg/L [interquartile range, IQR, 533–1644] vs 270 μg/L [IQR 153–558], P < 0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028 μg/L [IQR 1399–3556] vs 574 μg/L [IQR 526–943], P = 0.007). Furthermore, two microRNAs (miR‐122 and miR‐215) were downregulated in early hyperlactatemia (P = 0.019 and P = 0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r = 0.55) and lactate (r = 0.60).ConclusionsParacetamol overdose causes concentration‐related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity.

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“…Acetaminophen is a common household analgesic which is not considered harmful to gastric mucosa [7,8]. In vivo studies in rats showed that acetaminophen protects gastric mucosa against acidified aspirin and ethanol [9,10].…”

mentioning

confidence: 99%

Acetaminophen Directly Protects Human Gastric Epithelial Cell Monolayers against Damage Induced by Sodium Taurocholate

1988

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The present study evaluated whether acetaminophen can reduce sodium-taurocholate-induced damage to human gastric epithelial cells grown in monolayer culture (a preparation which excludes systemic factors). Further, the role of endogenous prostaglandin production by gastric cells in any such protection has been assessed. Results showed that (1) acetaminophen significantly protects human gastric epithelial cells against taurocholate-induced damage in vitro, in conditions independent of systemic factors, (2) protection of gastric cells by acetaminophen in vitro appears unrelated to stimulation of prostaglandin synthesis, and (3) a direct protective effect on gastric epithelial cells may play a role in protection of gastric mucosa by acetaminophen in vivo.

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Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man.

Cited by 19 publications

References 16 publications

Effect of cimetidine on ion fluxes and potential difference across the human stomach

Effect of cimetidine on ion fluxes and potential difference across the human stomach

Intestinal injury in paracetamol overdose (ATOM‐8)

Acetaminophen Directly Protects Human Gastric Epithelial Cell Monolayers against Damage Induced by Sodium Taurocholate

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