Launched in 2018, BSEP
is the invention of both Sharjah-based NAMA Women Advancement Establishment's education and capacity building arm, Badiri Education and Development Academy, and UK-based School for Social Entrepreneurs (SSE).
For the "BSEP
50" and "MMID 30" installations financing has been provided by the European Bank for Reconstruction and Development (EBRD), the Dutch Development Bank (FMO) and the Green Climate Fund (GCF).
In one recent study, the models for BSEP
, BCRP, P-glycoprotein and for OATP1B1 and 1B3 were investigated for their potential to improve the DILI-predicting algorithm.
These findings could be explained by bile acid levels inside the liver that are controlled by the action of BSEP
, which is the protein product of ABCB11 gene and is located at the hepatocyte canalicular membrane.
With cholestasis, not only is there reduced biliary excretion of bile, but, due to coregulation of BSEP
and MRP2, detoxification is impaired as well.
In vitro cell uptake and membrane vesicle efflux assays using [[sup.3]H] LCATD demonstrated that this amphiphilic molecule can hardly penetrate the cell membrane by passive diffusion, whereas it is quickly taken up by cells expressing the OATP1B1, NTCP transporters, and effluxed by means of BSEP
The transfer of BS from the liver to the bile canaliculus is determined by several transport proteins in the canalicular (apical) membrane of hepatocytes, mainly ATP-dependent BSEP
An inhibition of BSEP
function causes the accumulation of cytotoxic bile acids in hepatocytes, which induce oxidative stress and/or apoptosis and necrosis by FAS-mediated pathways.
MDRs, BCRP, BSEP
, and MRPs are all efflux transporters of the ABC family with clinical relevance in hepatotoxicity.
Paucity of bile ducts with ductular proliferation (10y) 10 188 0.6 -- 310 N/D * patient 3 had an initial platelets count of 102x10^3 [micro]L and a ceruloplasmin of 67 mg/dL; ** patient 8 had an initial platelets count of 78x10^3 [micro]L; Legend (for table 1 and 2): ALT=alanine aminotransferase (U/L), AST= aspartate aminotransferase (U/L), TB = total bilirubin ([micro]mol/L), DB= direct bilirubin ([micro]mol/L), GGTP = gamma-glutamyl transpeptidase (U/L), BSEP
= bile salt export pump, MRP2 = multidrug resistance-associated protein 2, OLT = orthotopic liver transplant, N/D = not done.
STEWART ROWLANDS Charity: Children's Liver Disease Foundation Why he's running: Stewart, 36, wanted to do something to raise money for the charity after his six-year-old nephew Adam was diagnosed with the rare liver disease BSEP
8, GW4064 treatment caused a significant increase in the mRNA level of phase II conjugation enzymes and phase III transporters, including glutathione S-transferases (GSTs) (Gst[alpha]3 and Gst[alpha]4) as well as GSH metabolism-related genes (Gclm, GpxJ), glucuronosyltransferase (Ugtlal), sulfotransferases (SultJal) (phase II), and efflux transporters (Mrp2 and Bsep
) (phase III).