Diclofenac and ibuprofen are associated with increased risk of cardiac arrest

Wise, Jacqui

doi:10.1136/bmj.j1358

BMJ

2017

DOI: 10.1136/bmj.j1358

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Diclofenac and ibuprofen are associated with increased risk of cardiac arrest

Jacqui Wise¹

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Activation of intestinal GR–FXR and PPARα–UGT signaling exacerbates ibuprofen-induced enteropathy in mice

Wang

et al. 2017

Arch Toxicol

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Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75 mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200 mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway. Instead, glucocorticoid receptor (GR) mediated the effect of DEX (5 mg/kg) on both the acute (200 mg/kg) and 7-day repeated-dose (50 mg/kg) toxicity of IBU in the small intestine. Combined treatment of DEX (5 mg/kg) and IBU (50 mg/kg) synergistically repressed the intestinal farnesoid X receptor (FXR)-cystathionine-γ-lyase signaling, which was accompanied with an elevation in the biliary excretion of bile acids, especially the FXR antagonist tauro-β-muricholic acid. DEX (5 mg/kg) also activated intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferase (UGT) pathway, which increased the formation and enterohepatic circulation of IBU-acyl glucuronide. Furthermore, DEX (5 mg/kg) and IBU (50 mg/kg) altered the intestinal microbial composition, characterized with a marked decrease in Actinobacteria. To conclude, the present study for the first time suggests that glucocorticoids play vital roles in control of IBU enteropathy via intestinal GR-FXR and PPARα-UGT signaling.

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Activation of intestinal GR–FXR and PPARα–UGT signaling exacerbates ibuprofen-induced enteropathy in mice

Wang

et al. 2017

Arch Toxicol

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Diclofenac and ibuprofen are associated with increased risk of cardiac arrest

Cited by 1 publication

References 1 publication

Activation of intestinal GR–FXR and PPARα–UGT signaling exacerbates ibuprofen-induced enteropathy in mice

Activation of intestinal GR–FXR and PPARα–UGT signaling exacerbates ibuprofen-induced enteropathy in mice

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