Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments
Abstract
:1. Introduction
2. Results and Discussion
2.1. Dose Optimization for Thioacetamide Exposure
2.2. Gene-Level Analysis
2.3. KEGG Pathway Analysis
2.4. Liver Injury Module Analysis
2.5. Hepatocyte Transporters and Cytochrome P450 Enzymes
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Cell Viability Assays
3.3. Experimental Procedures
3.4. Computational Details for RNA-Seq Data, KEGG Pathways, and Injury Module Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Overlap | 12 mM Thioacetamide | ||||
---|---|---|---|---|---|
Lots | A | B | C | D | E |
A | 2821 | 1631 | 1542 | 1302 | 1609 |
B | 3128 | 1970 | 1600 | 1567 | |
C | 3521 | 1548 | 1444 | ||
D | 2241 | 1275 | |||
E | 2347 |
Gene (Down) | log2(FC) | SD | Gene (Up) | log2(FC) | SD |
---|---|---|---|---|---|
CYP26B1 | −4.50 | 1.66 | C2CD4B | 2.42 | 0.39 |
CYP26A1 | −3.75 | 2.00 | C2CD4A | 2.40 | 0.27 |
IFNGR1 | −2.53 | 3.03 | SERPINA1 | 2.32 | 4.92 |
MCM10 | −2.15 | 0.78 | DDAH2 | 2.08 | 2.17 |
STEAP4 | −1.95 | 0.62 | THRSP | 1.85 | 0.52 |
GNAO1 | −1.75 | 1.74 | FGF21 | 1.81 | 0.22 |
SPP1 | −1.44 | 0.28 | PIWIL2 | 1.35 | 0.37 |
LPCAT1 | −1.44 | 1.12 | FUT1 | 1.32 | 0.23 |
DTL | −1.41 | 0.18 | SNORC | 1.26 | 0.08 |
WDR76 | −1.33 | 0.23 | SLCO4C1 | 1.21 | 0.35 |
KEGG Pathway (HD, 24 h) | Benjamini p-Value |
---|---|
Steroid biosynthesis | 9.4 × 10−6 |
Peroxisome | 6.5 × 10−5 |
Metabolic pathways | 1.3 × 10−3 |
Carbon metabolism | 4.8 × 10−3 |
Steroid hormone biosynthesis | 8.4 × 10−3 |
Glyoxylate and dicarboxylate metabolism | 9.2 × 10−3 |
Glycine, serine, and threonine metabolism | 1.2 × 10−2 |
Biosynthesis of cofactors | 1.2 × 10−2 |
Tight junction | 1.6 × 10−2 |
p53 signaling pathway | 2.0 × 10−2 |
Biosynthesis of amino acids | 2.4 × 10−2 |
Terpenoid backbone biosynthesis | 3.5 × 10−2 |
Ribosome biogenesis in eukaryotes | 5.0 × 10−2 |
Biosynthesis of unsaturated fatty acids | 7.0 × 10−2 |
DNA replication | 7.0 × 10−2 |
Lots | Gene Level Feature Sets | ||
---|---|---|---|
PTGS (All) | PTGS (Core) | TMG | |
A | 0.75 | 0.71 | 0.68 |
B | 0.80 | 0.78 | 0.70 |
C | 0.94 | 0.89 | 0.83 |
D | 0.88 | 0.80 | 0.79 |
E | 0.85 | 0.81 | 0.74 |
Drug Transporters | Names | Gene Symbol | A | B | C | D | E | Avg. | SD |
---|---|---|---|---|---|---|---|---|---|
Basolateral or sinusoidal uptake transporters | OATP1B3 | SLCO1B3 | 0.37 | −0.10 | −0.33 | −0.34 | 1.27 | 0.17 | 0.68 |
OATP2B1 | SLCO2B1 | 0.76 | 0.29 | 1.19 | 0.58 | −2.49 | 0.07 | 1.46 | |
OAT2 | SLC22A7 | 2.56 | −1.88 | −3.97 | −1.59 | 4.25 | −0.13 | 3.40 | |
OAT7 | SLC22A9 | 0.08 | 0.67 | 0.86 | 0.45 | 0.14 | 0.44 | 0.33 | |
OCT1 | SLC22A1 | 0.22 | −1.52 | 0.23 | 3.32 | 0.21 | 0.49 | 1.75 | |
Basolateral efflux transporters | MRP3 | ABCC3 | −0.24 | 0.63 | 1.45 | −0.65 | 0.97 | 0.43 | 0.86 |
MRP4 | ABCC4 | 0.24 | −1.81 | −1.57 | 2.19 | 0.37 | −0.11 | 1.63 | |
Canalicular efflux transporters | MRP2 * | ABCC2 | 0.24 | 0.37 | 0.25 | 0.32 | 0.30 | 0.30 | 0.06 |
FIC1 * | ATP8B1 | −0.22 | −0.36 | −0.55 | −0.49 | −0.16 | −0.36 | 0.17 | |
BCRP * | ABCG2 | 0.25 | 0.44 | 0.14 | 0.18 | 0.27 | 0.26 | 0.12 | |
Pgp (MDR1) | ABCB1 | 0.20 | −0.63 | 0.90 | 0.14 | 5.27 | 1.18 | 2.35 | |
MDR3 | ABCB4 | −0.41 | 0.37 | 0.85 | −2.17 | −0.48 | −0.37 | 1.15 | |
SLC transporters | SLC16A11 | 3.94 | 0.64 | 3.61 | 0.66 | 1.85 | 2.14 | 1.58 | |
SLC16A13 | 0.44 | 0.78 | 0.93 | 1.08 | 0.52 | 0.75 | 0.27 |
Gene Symbol | A | B | C | D | E | Avg. | SD |
---|---|---|---|---|---|---|---|
CYP2C9 | 0.33 | 0.36 | 1.16 | 0.90 | 0.14 | 0.58 | 0.43 |
CYP3A4 | 0.51 | 2.11 | 1.22 | 0.86 | 0.35 | 1.01 | 0.70 |
CYP3A5 | 1.05 | 0.87 | 0.87 | 0.91 | 0.90 | 0.92 | 0.07 |
CYP26A1 | −2.20 | −7.22 | −2.66 | −3.33 | −3.37 | −3.75 | 2.00 |
CYP26B1 | −2.98 | −5.48 | −4.07 | −3.10 | −6.86 | −4.50 | 1.66 |
CYP1A1 | 1.02 | 2.02 | 2.86 | 2.89 | −1.46 | 1.46 | 1.81 |
CYP1A2 | −0.20 | 0.68 | 0.14 | 0.60 | −0.12 | 0.22 | 0.40 |
CYP2C19 | 0.27 | 0.33 | 0.85 | 0.69 | 0.82 | 0.59 | 0.27 |
CYP2C8 | −0.63 | −0.29 | −0.28 | 3.45 | −0.38 | 0.37 | 1.73 |
CYP2E1 | 0.31 | 0.23 | 0.28 | 0.24 | 0.22 | 0.26 | 0.04 |
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Goel, H.; Printz, R.L.; Pannala, V.R.; AbdulHameed, M.D.M.; Wallqvist, A. Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments. Int. J. Mol. Sci. 2024, 25, 3265. https://doi.org/10.3390/ijms25063265
Goel H, Printz RL, Pannala VR, AbdulHameed MDM, Wallqvist A. Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments. International Journal of Molecular Sciences. 2024; 25(6):3265. https://doi.org/10.3390/ijms25063265
Chicago/Turabian StyleGoel, Himanshu, Richard L. Printz, Venkat R. Pannala, Mohamed Diwan M. AbdulHameed, and Anders Wallqvist. 2024. "Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments" International Journal of Molecular Sciences 25, no. 6: 3265. https://doi.org/10.3390/ijms25063265