PMID- 32562381
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20210701
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 8
IP  - 12
DP  - 2020 Jun
TI  - The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect 
      against intestinal inflammation by inhibition of epithelial apoptosis.
PG  - e14456
LID - 10.14814/phy2.14456 [doi]
LID - e14456
AB  - Increased epithelial permeability is a key feature of IBD pathogenesis and it has 
      been proposed that agents which promote barrier function may be of therapeutic 
      benefit. We have previously reported the secondary bile acid, ursodeoxycholic 
      acid (UDCA), to be protective in a mouse model of colonic inflammation and that 
      its bacterial metabolism is required for its beneficial effects. The current 
      study aimed to compare the effects of UDCA, LCA, and a non-metabolizable analog 
      of UDCA, 6-methyl-UDCA (6-MUDCA), on colonic barrier function and mucosal 
      inflammation in a mouse model of colonic inflammation. Bile acids were 
      administered daily to C57Bl6 mice by intraperitoneal injection. Colonic 
      inflammation, induced by addition of DSS (2.5%) to the drinking water, was 
      measured as disease activity index (DAI) and histological score. Epithelial 
      permeability and apoptosis were assessed by measuring FITC-dextran uptake and 
      caspase-3 cleavage, respectively. Cecal bile acids were measured by HPLC-MS/MS. 
      UDCA and LCA, but not 6-MUDCA, were protective against DSS-induced increases in 
      epithelial permeability and colonic inflammation. Furthermore, UDCA and LCA 
      inhibited colonic epithelial caspase-3 cleavage both in DSS-treated mice and in 
      an in vitro model of cytokine-induced epithelial injury. HPLC-MS/MS analysis 
      revealed UDCA administration to increase colonic LCA levels, whereas LCA 
      administration did not alter UDCA levels. UDCA, and its primary metabolite, LCA, 
      protect against intestinal inflammation in vivo, at least in part, by inhibition 
      of epithelial apoptosis and promotion of barrier function. These data suggest 
      that clinical trials of UDCA in IBD patients are warranted.
CI  - (c) 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on 
      behalf of The Physiological Society and the American Physiological Society.
FAU - Lajczak-McGinley, Natalia K
AU  - Lajczak-McGinley NK
AUID- ORCID: 0000-0002-1277-0761
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont 
      Hospital, Dublin 9, Ireland.
FAU - Porru, Emanule
AU  - Porru E
AD  - Department of Chemistry, University of Bologna, Bologna, Italy.
FAU - Fallon, Ciara M
AU  - Fallon CM
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont 
      Hospital, Dublin 9, Ireland.
FAU - Smyth, Jessica
AU  - Smyth J
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont 
      Hospital, Dublin 9, Ireland.
FAU - Curley, Caitriona
AU  - Curley C
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont 
      Hospital, Dublin 9, Ireland.
FAU - McCarron, Paul A
AU  - McCarron PA
AD  - School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, 
      Northern Ireland.
FAU - Tambuwala, Murtaza M
AU  - Tambuwala MM
AUID- ORCID: 0000-0001-8499-9891
AD  - School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, 
      Northern Ireland.
FAU - Roda, Aldo
AU  - Roda A
AUID- ORCID: 0000-0001-7649-4797
AD  - Department of Chemistry, University of Bologna, Bologna, Italy.
AD  - INBB, National Institute of Bio structures and Biosystems, Rome, Italy.
FAU - Keely, Stephen J
AU  - Keely SJ
AUID- ORCID: 0000-0002-6315-3587
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont 
      Hospital, Dublin 9, Ireland.
LA  - eng
GR  - 16-IA-4445/SFI_/Science Foundation Ireland/Ireland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Cholagogues and Choleretics)
RN  - 0 (Detergents)
RN  - 0 (Protective Agents)
RN  - 5QU0I8393U (Lithocholic Acid)
RN  - 724L30Y2QR (Ursodeoxycholic Acid)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cholagogues and Choleretics/pharmacology
MH  - Detergents/pharmacology
MH  - Disease Models, Animal
MH  - Inflammatory Bowel Diseases/*drug therapy/metabolism/pathology
MH  - Intestinal Mucosa/*drug effects/metabolism
MH  - Lithocholic Acid/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Permeability
MH  - Protective Agents/*pharmacology
MH  - Ursodeoxycholic Acid/*pharmacology
PMC - PMC7305237
OTO - NOTNLM
OT  - apoptosis
OT  - bile acid
OT  - colitis
OT  - epithelial barrier function
COIS- None declared.
EDAT- 2020/06/21 06:00
MHDA- 2021/07/02 06:00
PMCR- 2020/06/19
CRDT- 2020/06/21 06:00
PHST- 2020/04/02 00:00 [received]
PHST- 2020/04/08 00:00 [revised]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/06/21 06:00 [entrez]
PHST- 2020/06/21 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/06/19 00:00 [pmc-release]
AID - PHY214456 [pii]
AID - 10.14814/phy2.14456 [doi]
PST - ppublish
SO  - Physiol Rep. 2020 Jun;8(12):e14456. doi: 10.14814/phy2.14456.