Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Preparation and Characterization of LNPs
2.3. Animal Experiments
2.4. Serum and Liver Analysis
2.5. Liver Pathology
2.6. RNA Sequencing and Enrichment Analysis
2.7. Quantitative Real-Time Polymerase Chain Reaction (qPCR)
2.8. Western Blotting
2.9. Statistical Analysis
3. Results
3.1. Characterization and Validation of si-Cyp2e1 LNPs In Vivo
3.2. Immediate Treatment with si-Cyp2e1 LNPs Could Alleviate AILI in Mice
3.3. Transcriptomics Revealed the Possible Mechanism by Which si-Cyp2e1 LNPs Attenuate AILI in Mice
3.4. si-Cyp2e1 LNPs Could Regulate the PPAR Signaling Pathway
3.5. Delayed Treatment with si-Cyp2e1 LNPs for 2 h Did Not Ameliorate AILI in Time
3.6. si-Cyp2e1 LNPs Might Accelerate Liver Recovery Compared with NAC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
APAP | acetaminophen |
AILI | APAP-induced liver injury |
NAPQI | N-acetyl-p-benzoquinone imine |
CYPs | cytochrome P450 enzymes |
RNAi | RNA interference |
siRNA | small interfering RNA |
LNPs | lipid nanoparticles |
ALT | alanine aminotransferase |
AST | aspartate aminotransferase |
ROS | reactive oxygen species |
MDA | malondialdehyde |
SOD | superoxide dismutase |
GSH | glutathione |
H&E | hematoxylin and eosin |
DEGs | differentially expressed genes |
GO | Gene ontology |
KEGG | Kyoto encyclopedia of genes and genomes |
GSEA | gene set enrichment analysis |
qPCR | quantitative real-time polymerase chain reaction |
GAPDH | glyceraldehyde-3-phosphate dehydrogenase |
PPAR | peroxisome proliferator-activated receptor |
CD36 | cluster of differentiation 36 |
FABP1 | fatty acid binding protein 1 |
IL | interleukin |
TNF | tumor necrosis factor |
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Name | Size (nm) | Polydispersity Index | Zeta Potential (mV) | Encapsulation Rate (%) |
---|---|---|---|---|
si-Cyp2e1 LNPs | 78.04 ± 0.29 | 0.143 ± 0.031 | −0.45 ± 0.1 | 89.05 ± 0.38 |
si-Control LNPs | 72.47 ± 2.00 | 0.144 ± 0.013 | −0.37 ± 0.1 | 85.86 ± 1.07 |
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Liu, W.; Huan, L.; Zhang, C.; Yin, R.; Ouyang, Z.; Wei, Y. Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo. Curr. Issues Mol. Biol. 2025, 47, 372. https://doi.org/10.3390/cimb47050372
Liu W, Huan L, Zhang C, Yin R, Ouyang Z, Wei Y. Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo. Current Issues in Molecular Biology. 2025; 47(5):372. https://doi.org/10.3390/cimb47050372
Chicago/Turabian StyleLiu, Wenwen, Liwen Huan, Cai Zhang, Runting Yin, Zhen Ouyang, and Yuan Wei. 2025. "Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo" Current Issues in Molecular Biology 47, no. 5: 372. https://doi.org/10.3390/cimb47050372
APA StyleLiu, W., Huan, L., Zhang, C., Yin, R., Ouyang, Z., & Wei, Y. (2025). Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo. Current Issues in Molecular Biology, 47(5), 372. https://doi.org/10.3390/cimb47050372