Table 4

Summary of the results on the 18 tested drugs

Bile canaliculi deformation (i.e., constriction or dilatation), BSEP inhibition (vesicles), [³H]-TCA clearance (control = 100%), BSEP mRNA expression (control = 1), MLC2 phosphorylation state, and MLCK/ROCK implication are summarized. Human BSEP inhibition levels in transfected vesicles are taken from the literature and expressed as high (++), medium (+), and low (−) or absent.

Drug	Bile Canaliculi Deformation	BSEP Inhibition, Vesicles	[³H]-TCA Clearance (Control = 100%)	BSEP mRNA Expression (Control = 1)	MLC2 Phosphorylation State	MLCK/ROCK Implication
Group 1: drugs involved in clinical cholestasis
BOS	Dilatation	++^{^a}^,^{^b}^,^{^c}^,^{^d}	64.24 ± 4.13**	0.10 ± 0.01***	Dephosphorylation	MLCK
CPZ	Constriction	+^{^a}^,^{^c}^,^{^d}	49.96 ± 5.14^*	0.5 ± 0.2^*	Phosphorylation	ROCK
CsA	Constriction	++^{^a}^,^{^b}^,^{^c}^,^{^d}	13.16 ± 1.48**	0.54 ± 0.15**	Phosphorylation	ROCK
NEF	Constriction	++^{^a}^,^{^b}^,^{^c}^,^{^d}	52.46 ± 3.87***	0.28 ± 0.08^*	Phosphorylation	ROCK
TRO	Constriction	++^{^a}^,^{^b}^,^{^c}^,^{^d}	21.97 ± 3.72***	0.58 ± 0.11^*	Phosphorylation	ROCK
Group 2: drugs involved in rare cases of clinical cholestasis
CIM	Dilatation	+^{^a}	86.25 ± 12.12	0.33 ± 0.04***	Dephosphorylation	MLCK
DIC	Dilatation	+^{^a}^,^{^d}	384.8 ± 57.96**	0.66 ± 0.1^*	Dephosphorylation	MLCK
ENT	Dilatation	−^{^b}^,^{^d}	109.2 ± 16.94	0.83 ± 0.18	Dephosphorylation	MLCK
MET	Constriction	−^{^a}^,^{^d}	99.41 ± 8.45	0.30 ± 0.06***	Phosphorylation	ROCK
PER	Constriction	−^{^d}	41.43 ± 8.22**	0.45 ± 0.09^*	Phosphorylation	ROCK
TAC	Dilatation	−^{^b}	56.14 ± 2.71***	0.44 ± 0.11**	Dephosphorylation	MLCK
TOL	Dilatation then constriction	+^{^b}^,^{^c}^,^{^d}	48.36 ± 8.14**	0.20 ± 0.04***	No change	MLCK - ROCK
Group 3: drugs not involved in clinical cholestasis
AMI	No change	+^{^a}^,^{^b}^,^{^d}	115.6 ± 15.62	1.34 ± 0.19	No change	—
APAP	No change	−^{^c}^,^{^d}	137.2 ± 24.33	0.63 ± 0.14	No change	—
BUS	No change	−^{^a}^,^{^c}^,^{^d}	86.07 ± 13.39	0.32 ± 0.03**	No change	—
FIA	No change	−^{^d}	91.34 ± 9.14	0.66 ± 0.08	No change	—
PIO	No change	+^{^a}^,^{^b}^,^{^c}^,^{^d}	86.15 ± 3.34	0.66 ± 0.08	No change	—
XIM	No change	−^{^d}	96.71 ± 10.91	1.19 ± 0.16	No change	—

↵^a Pedersen et al. (2013).
↵^b Morgan et al. (2010).
↵^c Dawson et al. (2012).
↵^d P. Krajcsi (unpublished data).
↵* P < 0.01; **P < 0.05; ***P < 0.001.
—, no implication.