In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells

Dial, Elizabeth J.; Dawson, Paul A.; Lichtenberger, Lenard M.

doi:10.1152/ajpgi.00322.2014

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…As the most hydrophilic bile acid, UDCA is almost non-toxic. The common types of free and conjugated bile acids in the human body are in the order of hydrophilicity: UDCA CA CDCA DCA LCA, taurine-conjugated bile acid glycine-conjugated bile acid free bile acid [8] .…”

Section: Discussionmentioning

confidence: 99%

Maternal Bile Acid Profile and Subtype Analysis of Intrahepatic Cholestasis of Pregnancy

Shao

Tang

et al. 2020

SSRN Journal

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Background ICP pregnant women have a unique pro le of serum bile acid metabolis, early and accurate identi cation of ICP patients is bene cial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid pro les of ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and were divided into four subgroups according to serum levels of TBA, DBIL, and ALT. Results The differential serum bile acid pro les of ICP group and normal pregnant women were DCA, TDCCA, TCA, GDCA and GLCA. The differential serum bile acid pro les of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA. The differential serum bile acid pro les of the ICP3 group (hyperbiliary acidemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P <0.05). The differential serum bile acid pro les of ICP4 group (idiopathic aminotransferase abnormality during pregnancy) and normal pregnant group was UDCA, GUDCA, TUDCA, GCA and GLCA (P <0.05). The occurrence of meconium-stained amniotic uid, premature delivery and cesarean section in ICP1 group was signi cantly higher than normal group,ICP2 group,ICP3 group,and ICP4 group (P <0.05); The occurrence of meconium-stained amniotic uid, premature delivery and cesarean section in ICP2 group, ICP3 group,and ICP4 group was signi cantly higher than normal group (P <0.05), but no difference was found among ICP2 group, ICP3 group,and ICP4 group (P> 0.05). Conclusion: Maternal serum bile acid pro les are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

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Section: Discussionmentioning

confidence: 99%

Maternal Bile Acid Profile and Subtype Analysis of Intrahepatic Cholestasis of Pregnancy

Shao

Tang

et al. 2020

SSRN Journal

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“…Other methods to prevent NSAID injury to the intestine that remain to be fully tested include the use of lowertoxicity COX-2 inhibitors, prostaglandins, antimicrobials and probiotics (Lim and Chun 2013), and NSAIDs modified by the addition of H 2 S (Wallace et al 2010(Wallace et al , 2015 or phosphatidylcholine (PC) (Lanza et al 2008;Lichtenberger et al 2009a,b;Wallace et al 2010;Blackler et al 2012;Dial et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…BDL could be blocking a substantial amount of INDO from reaching the intestinal mucosa through the bile, but there is still INDO in the systemic circulation. Additionally, we have proposed that bile acids and INDO can form toxic mixed micelles within the bile fluid that contribute to INDO-induced GI injury (Zhou et al 2010;Dial et al 2015). This possibility is partially supported by others (Jacob et al 2007) who confirmed that INDO does not induce macroscopic intestinal injury in bile duct-ligated rats, while they also found that an oral dose of a bile acid, when mixed with INDO, failed to produce intestinal per- meability changes in BDL rats, suggesting that there is another component of bile secretion that is important for GI injury.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci

et al. 2016

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NSAID use is limited due to the drugs’ toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced by NSAIDs is dependent on bile secretion and is reported to increase the growth of a number of bacterial species, including an enterococcal species, Enterococcus faecalis. This study examined the relationships between indomethacin (INDO)‐induced intestinal injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci, and the contribution of bile secretion to these pathological responses. Rats received either a sham operation (SO) or bile duct ligation (BDL) prior to administration of two daily subcutaneous doses of saline or INDO, and 24 h later, biopsies of ileum and liver were collected for plating on selective bacterial media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess intestinal bleeding. Of the four treatment groups, only SO/INDO rats experienced a significant 10‐ to 30‐fold increase in fecal Hb and reduction in Hct, indicating that BDL attenuated INDO‐induced intestinal injury/bleeding. Ileal enterococcal colony‐forming units were significantly increased (500‐ to 1000‐fold) in SO/INDO rats. Of all groups, only the SO/INDO rats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated that INDO‐induced intestinal injury and E. faecalis overgrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with the NSAID. Bile secretion plays an important role in INDO‐induced gut injury and appears to support enterococcal overgrowth of the intestine. NSAID‐induced enterococcal SBO may be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis.

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“…It was reported that the toxicity of NSAID administrated as complexes with DPPC or related phospholipids was remarkably decreased whereas their antipyretic and anti-inflammatory activities enhanced [ 54 ]. In the research group of Lichtenberger, it has been proven that the pre-association of indomethacin with PC in the drug formulation prevents indomethacin from associating with mucus PC and disruption of its surface [ 55 ].…”

Section: Novel Strategies For Indomethacin Deliverymentioning

confidence: 99%

Lipid Formulations and Bioconjugation Strategies for Indomethacin Therapeutic Advances

Gliszczyńska

Nowaczyk

2021

Molecules

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Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, despite its high therapeutic efficacy in relieving the symptoms of certain arthritis and in treating gout or collagen diseases, administration of IND causes a number of adverse effects, such as gastrointestinal ulceration, frequent central nervous system disorders and renal toxicity. These obstacles significantly limit the practical applications of IND and make that 10–20% of patients discontinue its use. Therefore, during the last three decades many attempts have been made to design novel formulations of IND aimed to increase its therapeutic benefits minimizing its adverse effects. In this review we summarize pharmacological information about IND and analyze its new lipid formulations and lipid bioconjugates as well as discuss their efficacy and potential application.

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In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells

Abstract: Dial EJ, Dawson PA, Lichtenberger LM. In vitro evidence that phosphatidylcholine protects against indomethacin/bile acidinduced injury to cells.

Cited by 12 publications

References 23 publications

Maternal Bile Acid Profile and Subtype Analysis of Intrahepatic Cholestasis of Pregnancy

Maternal Bile Acid Profile and Subtype Analysis of Intrahepatic Cholestasis of Pregnancy

Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci

Lipid Formulations and Bioconjugation Strategies for Indomethacin Therapeutic Advances

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