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. 2017 Mar 7;18(3):574. doi: 10.3390/ijms18030574

Table 4.

Significant gene expression changes in human liver slices exposed daily for 48 h to APAP (1 mM), DCF (1 mM), MMI (500 μM), TBF (100 μM), CBZ (100 μM), ETM (100 μM), DTL (10 μM), CSA (10 μM). Values represent the fold change for the highest ranked genes (FDR = 15%) in human liver slices (N = 3 donors, n = 10 control and 6 treated slices/drug/donor).

Genes APAP DCF MMI TBF CBZ ETM DTL CSA
HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871 HL869 HL870 HL871
Metabolism
POR 2.5 3.5 3.0 2.8
CYP1A1 7.8 2.6 4.5 2.3 2.2 1.6 −1.6 8.5 8.1
CYP1A2 −1.7 1.6 −70.0 3.8 2.6 2.9 2.3 2.8 9.6 7.4
CYP2B6 1.7 2.4 −22.2 2.2 −4.5 2.9
CYP2C9 −4.9
CYP2C19 −6.3 −2.1 −28.6 2.0 −4.0 3.2 3.0 −4.4 1.8
CYP2D6 −1.9
CYP2E1 −1.7 −6.2
CYP3A4 8.4 −11.1 1.7 10.5 3.0 1.9 −8.7 −5.5 4.7
FMO3 −1.4 −1.8 −6.3 −1.6
FMO4 −4.0 −3.2 −6.4
FMO5 −7.2
Oxidative Stress
AASS −2.6 −2.3 −17.4
BDH2 −5.4 −2.6
GSTA3 −3.1 −34.4 2.0 −2.3 3.4 −4.4 −2.0
GSTM4 −3.5 −3.1 −7.5 1.9 −6.5
GPX1 −3.4
GPX2 1.5 −15.9 2.9 1.8 2.6 1.5 −1.6 −2.0 −1.8 −3.4
GPX3 −1.6 2.1 3.1 2.2 −2.3
GPX5 2.3 2.7
GPX6 2.3
CAT 1.6 −8.0
EPHX1 1.6 −2.2 −2.5 −8.9 2.5 1.8 1.6
DUOX1 −3.1 2.3 1.8 2.5
DUOX2 −2.3 4.1 −2.1 4.3 2.9
NQO1 1.9 2.9 2.6
NUDT15 −2.1 2.0 −1.8
PPP1R15B 7.3 2.0 3.9 26.4 8.2 −2.0 9.3 7.5 8.2 8.6
PRDX1 3.7 3.2 3.1
TXNIP −1.6 −1.9 2.8
CTSB 3.6 −4.4
Mitochondria Energy
ACO1 −1.7 −2.6 −3.7 −2.5 −2.1 −2.9
ACO2 −1.5
ACLY 2.3
ADK −5.8
CYC1 1.4 1.3
COX8A −6.1
DLD −27.3
IDH1 −1.7
IDH2 −1.7 −1.7
IDH3B 1.3 −1.8
MDH1 −1.5 3.1 3.1 −1.9 3.6 −2.9 −4.2 3.6 −1.9
SDHC −5.7 −1.7
SUCLA2 −10.3
SUCLG1 −1.4 3.3 −4.1
UCP2 −2.4 −2.9 −5.1
Heat Shock, ER Stress
HSPA2 −2.9 2.4
HSPA4 1.8 1.9
HSPA8 −1.9
HSPA9 1.3 2.1 3.6 2.1
HSPA1A −1.9
HSPA1B −2.2 −1.8
HSP90AA1 1.5 −1.5
HSP90B1 4.3 2.5 2.0 10.9 −1.9 −25.2 −2.1 3.9 −1.6 1.9 6.4
HSPB1 −2.6
HSPB6 2.3
HSPB8 3.3 −2.9 2.6
HSPD1 1.8 1.9 −2.1
HSPE1 −1.8 −1.6 −3.3
HSF2 8.0 −8.8
HSPH1 −7.7 −1.8
HERPUD1 7.0 −1.8 −2.0
SEC62 −2.1 6.4 7.2 −3.4 7.9 −4.6 5.7 −2.7 9.6
SEL1 2.0
SEL1L 4.4 2.5 2.6 12.8 5.1 4.2 −1.6 6.9
SELS 1.7 1.8
SERP1 −2.7 2.4 3.2 7.1 3.4 −3.2 −2.7 −2.3 −4.3 3.6 6.2
ATF4 3.4 5.1 3.3 2.1 1.5
ATF6 2.3 2.6 2.8
CRYAA −8.5
CRYAB 1.9 2.8 −2.9 3.2 −3.4 −1.8 −3.8
DDIT3 −1.9 4.9 16.3 24.8 −1.8
DNAJB1 −3.9 −1.5
DNAJB6 1.4 2.3 1.4
DNAJC3 −1.7 2.4
CNAJC5 2.0
DNAJC6 2.3 2.9 8.6 5.5 −3.1 −2.3
DNAJA1 −1.4
DNAJA2 1.4 1.4
DNAJA3 2.1 2.0
DERL1 3.5 3.8 2.8
EDEM1 2.5
EIF2AK3 3.4 5.8 11.5 2.9
ERO1LB 5.9 −1.6 1.9
MBTPS2 2.4 −2.4 2.4 −1.5 −2.5
NUCB1 −2.1
OS9 2.4
SYVN1 2.5 2.3 2.2
TCP1 1.2
UBE2G2 1.6 2.5
UBQLN2 −2.8
XBP1 −1.6
Fatty Acid Metabolism
ACAA1 −2.2 4.7 1.8 −34.0 −2.8
ACAA2 2.4 −5.9 −2.5
ACADM −1.9 3.2 1.9 −2.1 3.4 4.1 −5.2 2.5
ACADSB −7.3 1.7 −6.1
ACADL 2.3 −7.2
ACADVL 2.7 1.7 3.3 1.8 1.9
ACAT1 −6.2
ACAT2 −1.9 −2.1 −3.5 −4.3 −2.2
ACOT1 2.3
ACOT6 −6.9
ACOT7 −17.9
ACOT8 1.6
ACOT9 −7.8
ACOT12 −1.4 −3.9 1.6 −11.2
ACOX1 1.8 −8.4
ACOX2 −5.9 −4.4 −12.5 1.5 −8.2
ACOX3 1.6
CPT1A 2.1 8.1 1.5 2.1 16.1 2.4 2.3 2.5
APOA5 −8.1
APOE −1.8 −1.7 3.3 3.4
APOF −2.2 −5.5 −5.2 −8.7 −4.9 −1.7
DECR1 −5.8
ECHS1 −4.9 −2.4
EHHADH −14.7 1.6 −5.4 −1.8
HADHA 2.1 3.3 1.5 −3.1 −1.5
HADHB 3.2 −2.3 −2.3
ALB −1.5 1.4 −3.8 −7.6
Steatosis, Cholestasis, Phospholipidosis
ABCB1 1.5 2.8 2.8 4.1 2.2 1.5 −21.1
ABCB4 −1.5 −1.5 −2.2 −1.6 −25.8 −2.0
ABCC1 2.7
ABCC2 1.7 2.4 2.6 3.2 2.5 1.6 1.9
ABCC3 1.7 3.7 1.6 3.3 2.0 3.7
OSTβ −2.7 5.2 −2.4
AQP −10.9
AQP4 −2.6
ACACA 2.6 2.1 1.9
SLCO1A2 −28.9 −7.9 −20.9 2.1 1.8
SLC2A3 2.5
SLC10A1 −18.3 −2.6
ADH1C −11.3 −9.1 −7.4 −7.0 3.3
ALDH1A1 1.9 −2.4 −3.5 −10.7 2.2 2.5 1.6 −4.6
ALDH2 −5.7
ASAH1 −5.7
ASNS 6.6 7.4 4.4 2.9
CYP7A1 3.0 −51.1 4.7 −4.5 −3.3 2.3 −19.4 4.5 3.9
CYP7B1 −2.8 6.0 4.8 6.4 4.6 4.9 −14.3 6.6
CD36 2.4 −5.2
COMT −5.2
DNM1 2.4
ENO1 1.8
FABP1 −2.3 −1.6 −2.3 −22.0 −1.7 −3.5 7.2 −3.2 5.6 −1.5 −4.3 −3.4
FASN −2.2
FXC1 2.5 4.0 2.5
GPD1 −1.7 2.1 1.9 −1.8 1.9
HAAO −14.1
HLA−DRB1 −2.6
ICAM1 −15.8 −2.1
INHBE 2.7
KHK −4.2 −2.4
LPL 1.9 3.1 2.9 4.4 4.5
MTTP −2.8 −5.7 −11.5
NR0B2 −1.5
NR1H4 −2.1
PCCA 3.6 5.1 3.7 8.5 5.2
PNPLA3 −2.6
RDX −12.6
SCD −2.9 3.9 −4.1
SREBF1 −3.4 −3.7
SC4MOL 3.3 −1.6 6.8 −1.9 6.4 6.0 6.6 −2.3
S100A8 −6.5
TAGLN 2.0
TGFB1 −4.8 −1.9
UGT1A1 3.3 1.9 1.8 −4.3
UGT2A1 2.3
UGT2B4 2.1 11.4 2.2 4.5 2.7 −3.9 6.0 4.1 5.8 −3.2 4.9
WIPl1 2.9 4.0 6.7 1.8
DNA damage, repair
AHR −5.2
APEX1 −5.1
BRCA1 3.2
BRCA2 1.8 3.2 2.8 −2.0
CDKN1 2.1 3.8 3.3 −4.6 −2.4
CDKN1A −3.2
CHEK1 1.8 −1.9
CHEK2 −8.4 −4.2 −2.3 −2.3
DDIT3 −1.6
ERCC1 4.6 2.5 3.8 24.6 6.7 6.7 2.5 7.8 −2.1 8.4
ERCC6 −1.8
HPRT1 1.4
MGMT 1.5
MLH1 2.1
MSH2 3.9 −2.6 3.5 3.4 −1.7 3.2 −4.4 3.6
OGG1 1.6
POU3F3 2.3
PRKDC −2.9 −2.2
RAD51 −2.9
XPA −3.3
Apoptosis
AKT1 2.1
APAF1 2.2
BAK1 −6.0
BID 2.8 1.4 2.3
BIRC3 −1.7 −2.0
BCL2L1 2.2 −1.9
BCL2L11 −1.9
CASP1 −4.7 −1.6
CASP3 −3.9
CASP8 2.4 1.6
FADD 2.5 2.1 3.3 6.8 2.7 1.8 2.9 2.2 2.7 2.2 2.9
FAS 5.4 11.0 8.3 −2.5 8.0 5.5 −3.1 6.9 7.6
FASLG −2.1 −8.3 2.1
GADD45A 2.5 11.5 30.7 −3.5 −3.9 −8.0
MK167 −4.7 −30.7 −2.5 −4.3 −3.1 −3.7 −5.9 −4.6 −27.7
TNFSF10 −5.0 −12.0 −24.8 −2.6
TNFRSF10A 3.8 2.7 6.3 2.7 2.2 2.5
TNFRSF10B 2.9 3.6 4.1
XIAP 2.0 2.4 5.5 −7.9 3.3 2.8 3.3
Necrosis
ATP6V1G2 −3.2 −2.5
BMF 2.8 2.2 2.2
CYLD 4.2
DEFB1 −2.6
EIF5B 1.9 −4.3
FOXl1 2.3
GALNT5 2.3
HOXA3 2.2
JPH3 2.3
KCNIP1 2.3
NUDT13 −3.4 3.9 2.6 3.0 2.8 2.9 4.8
PVR 2.4
RAB25 −2.9 −2.2
TMEM57 −16.2 1.8
TNFAIP8L1 2.6 −2.0
S100A7A 2.3
Immune Response, Inflammation
AHSG −2.0 −3.4 −4.2 −1.7 −2.4
IL1A 2.2
IL1B −2.9 −10.2 −2.5 −3.5 −2.4 −8.2 −3.9
IL2 2.4
IL4 56
IL6 −2.5 −4.2 −4.9
IL10 2.8
C3 −1.9 −33.3 −1.8
C9 −6.3 −3.8 −7.6 2.0
CD4 2.8 −2.8
CD80 2.2 1.6 1.8 −5.7
CD86 2.5 −4.5
CTSE 2.1 −2.9
EP300 2.2 2.5 2.2 2.5
HRG 4.1 −3.3
HRT2A 2.1 2.1 2.3
IFNG 2.6 −2.4 −3.3
KLF1 −2.2
LY6D 2.6
LYZ −2.2 −4.9 −2.6 −1.9 −1.9
PON1 −1.7 −7.0 1.8 −2.5
PTGS2 16.9 34.8 −2.1
SOD1 1.5
TRIM10 4.0 4.1 3.9 3.3 3.6