scholarly journals Quantitative systems toxicology (QST) reproduces species differences in PF‐04895162 liver safety due to combined mitochondrial and bile acid toxicity

2019 ◽  
Vol 7 (6) ◽  
Author(s):  
Grant Generaux ◽  
Vinal V. Lakhani ◽  
Yuching Yang ◽  
Sashi Nadanaciva ◽  
Luping Qiu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Species Differences ◽  
Systems Toxicology ◽  
Liver Safety ◽  
Quantitative Systems Toxicology ◽  
Acid Toxicity

scholarly journals Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity

2018 ◽  
Vol 166 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Christina Battista ◽  
Kyunghee Yang ◽  
Simone H Stahl ◽  
Jerome T Mettetal ◽  
Paul B Watkins ◽  
...  
Keyword(s):  
Species Differences ◽  
Systems Toxicology ◽  
Quantitative Systems Toxicology

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

scholarly journals Regional Differences in the Components of Luminal Water from Rat Gastrointestinal Tract and Comparison with Other Species.

2012 ◽  
Vol 15 (4) ◽  
pp. 510 ◽  
Author(s):  
Yusuke Tanaka ◽  
Toshihiro Hara ◽  
Ryoichi Waki ◽  
Shunji Nagata
Keyword(s):  
Bile Acid ◽  
Regional Differences ◽  
Species Differences ◽  
Oral Absorption ◽  
Inorganic Ions ◽  
Total Bile Acid ◽  
Water Soluble ◽  
Residual Water ◽  
Gi Tract ◽  
Water Soluble Drug

Purpose. The bile acids, phospholipids, inorganic ions, and pH in luminal fluid are very important factors for the dissolution and oral absorption of solid drugs. In this study, we evaluated the regional differences in these factors in the rat GI tract. The solubility of griseofulvin, a poorly water-soluble drug, in the luminal fluid in each segment was also measured. In addition, the data from rats were compared with those from other species published previously to evaluate the species differences in the composition of luminal fluid. Methods. Rat abdomen was opened and residual water was sampled from each region of GI tract to measure the various components concentrations. Results. The total bile acid and phospholipid concentrations were much higher in the lower jejunum and upper jejunum, respectively, than in the other regions. The solubilities of griseofulvin in the lower jejunal fluid (153-260 g/mL) were about 1.5-2 times higher than those in the upper jejunal fluid (99-146 g/mL). The regional differences in inorganic ions and pH were also observed. As for species differences, the total bile acid and phospholipid concentration in rats GI tract were much higher than those of dogs and humans. Conclusion. These informations about the regional differences and species differences of the components in the GI fluid should be very useful to consider dissolution and oral absorption of solid drugs.

96 KNOCKOUT OF THE PSC RISK GENE FUT2 SENSITIZES MICE TO HEPATO-BILIARY BILE ACID TOXICITY

2013 ◽  
Vol 58 ◽  
pp. S42 ◽  
Author(s):  
L. Maroni ◽  
D. Tolenaars ◽  
T.H. Karlsen ◽  
R. Oude Elferink ◽  
U. Beuers
Keyword(s):  
Bile Acid ◽  
Biliary Bile Acid ◽  
Risk Gene ◽  
Acid Toxicity

scholarly journals Quantitative systems toxicology

2017 ◽  
Vol 4 ◽  
pp. 79-87 ◽  
Author(s):  
Peter Bloomingdale ◽  
Conrad Housand ◽  
Joshua F. Apgar ◽  
Bjorn L. Millard ◽  
Donald E. Mager ◽  
...  
Keyword(s):  
Systems Toxicology ◽  
Quantitative Systems Toxicology
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