Interaction between aspirin and paracetamol on the production of prostaglandins in the rat gastric mucosa

Kolfschoten, A. A. van; Dembińska-Kieć, A.; Basista, M

doi:10.1111/j.2042-7158.1981.tb13834.x

Cited by 21 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, Garcia Rodriguez & Hernadez‐Diaz (2001) have shown that similarly to oral steroids and aspirin, acetaminophen use was associated with a 2 fold increased risk of upper GI complications when taken at daily doses 2 g. This effect might be due to an inhibitory action of acetaminophen on gastric prostanoid biosynthesis (Konturek et al ., 1981). However, this finding has been contradicted by other studies that have shown no effect or even an increase of gastric PGE 2 biosynthesis by acetaminophen (Peskar, 1977; van kolfschoten et al ., 1981).…”

Section: Discussionmentioning

confidence: 99%

Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells

Sciulli

Seta

Tacconelli

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

1 Acetaminophen, an analgesic and antipyretic drug with weak antiin¯ammatory properties, has been suggested to act as a tissue-selective inhibitor of prostaglandin H synthases (PGHSs) (e.g. COX-1 and COX-2) through its reducing activity, that is in¯uenced by the di erent cellular levels of peroxides. 2 We have studied the e ects of acetaminophen on inducible and constitutive prostanoid biosynthesis in monocytes and platelets in vitro. To discriminate between the inhibitory e ect of the drug on PGHS-isozymes vs PGE-synthases (PGESs), parallel measurements of PGE 2 and thromboxane (TX) B 2 were carried out. Since antioxidant enzymes and cofactors, present in plasma, may a ect acetaminophen-dependent inhibition of prostanoids, comparative experiments in whole blood vs isolated monocytes were performed. 3 Acetaminophen inhibited LPS-induced whole blood PGE 2 and TXB 2 production, in a concentration-dependent fashion [IC 50 mM (95% con®dence intervals): 44 (27 ± 70) and 94 (79 ± 112), respectively]. Therapeutic plasma concentrations (100 and 300 mM) of the drug more profoundly reduced PGE 2 than TXB 2 (71+3 vs 54+4 and 95+0.8 vs 78+2%, respectively, mean+s.e.mean, n=6, P50.01). 4 Di erently, in isolated monocytes stimulated with LPS, both PGE 2 and TXB 2 production was maximally reduced by only 60%. 5 At 100 and 300 mM, the drug caused a similar and incomplete inhibition of platelet PGE 2 and TXB 2 production during whole blood clotting (45+4 vs 54+4 and 75+2 vs 75+1%, respectively, mean+s.e.mean, n=4). 6 In conclusion, therapeutic concentrations of acetaminophen caused an incomplete inhibition of platelet COX-1 and monocyte COX-2 but in the presence of plasma, the drug almost completely suppressed inducible PGE 2 biosynthesis through its inhibitory e ects on both COX-2 and inducible PGES.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells

Sciulli

Seta

Tacconelli

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…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%

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

Nakamoto

Kamisaki²,

Wada³

et al. 1997

Pharmacology

View full text Add to dashboard Cite

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.

show abstract

“…However, the effects on IBP-induced gastric damage were limited because the suppression by APAP was examined in a fixed dose (Van Kolfschoten et al, 1983). Various theories have been proposed to explain the gastroprotective effects of APAP, such as activation of PG synthesis and scavenging of free radicals (van Kolfschoten et al, 1981). However, the precise mode of action has not yet been completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase

Fukushima

Monoi

Mikoshiba

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofeninduced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1b (IL-1b), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofeninduced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.

show abstract

Interaction between aspirin and paracetamol on the production of prostaglandins in the rat gastric mucosa

Cited by 21 publications

References 9 publications

Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells

Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells

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

Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase

Contact Info

Product

Resources

About