Advances in drug-induced cholestasis: Clinical perspectives, potential mechanisms and in vitro systems
Por:
Fernandez-Murga, M, Petrov, P, Conde, I, Castell, J, Gomez-Lechon, M and Jover, R
Publicada:
1 oct 2018
Resumen:
Despite growing research, drug-induced liver injury (DILI) remains a serious issue of increasing importance to the medical community that challenges health systems, pharmaceutical industries and drug regulatory agencies. Drug-induced cholestasis (DIC) represents a frequent manifestation of DILI in humans, which is characterised by an impaired canalicular bile flow resulting in a detrimental accumulation of bile constituents in blood and tissues. From a clinical point of view, cholestatic DILI generates a wide spectrum of presentations and can be a diagnostic challenge. The drug classes mostly associated with DIC are anti-infectious, anti-diabetic, anti-inflammatory, psychotropic and cardiovascular agents, steroids, and other miscellaneous drugs. The molecular mechanisms of DIC have been investigated since the 1980s but they remain debatable. It is recognised that altered expression and/or function of hepatobiliary membrane transporters underlies some forms of cholestasis, and this and other concomitant mechanisms are very likely in DIC. Deciphering these processes may pave the ways for diagnosis, prognosis and prevention, for which currently major gaps and caveats exist. In this review, we summarise recent advances in the field of DIC, including clinical aspects, the potential mechanisms postulated so far and the in vitro systems that can be useful to investigate and identify new cholestatic drugs.
Filiaciones:
:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Petrov, P:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Conde, I:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Castell, J:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Valencia, Fac Med, Dept Bioquim & Biol Mol, Valencia, Spain
Gomez-Lechon, M:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Jover, R:
IIS La Fe, Unidad Hepatol Expt, Ave Fernando Abril Martorell,106 Torre A, Valencia 46026, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Valencia, Fac Med, Dept Bioquim & Biol Mol, Valencia, Spain
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