Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Recombinant EC-SOD
2.2. Animals and Treatment
2.3. Blood and Urine Parameters
2.4. Histological Assessment
2.5. Western Blot Analysis
2.6. In Vitro Study
2.7. Statistical Analysis
3. Results
3.1. Characteristics of Experimental Mice Groups
3.2. Effects of hEC-SOD on Intrahepatic Histologic Changes Associated with Fibrosis, Inflammation and Lipid Accumulation
3.3. Intrahepatic SOD Isoforms and SOD3 Expression in Response to hEC-SOD Treatment
3.4. Effects of hEC-SOD on Intrahepatic Expression of Phospho/Total AMPK and Associated Downstream Signaling Pathways including Phospho-/Total FoxOs and PGC-1α
3.5. Effects of EC-SOD on Intrahepatic Expression of Perilipin-2, PPARα/γ, Phospho-ACC and SREBP-1c
3.6. Effect of EC-SOD on Intrahepatic Expression of Bcl-2, BAX, Beclin-1 and LC3
3.7. Inflammatory Cytokines and Cellular Alterations in the Liver Following EC-SOD Treatment
3.8. In Vitro Studies (HepG2)
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Correction Statement
References
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Variables | db/m Control | db/m hEC-SOD | db/db Control | db/db hEC-SOD |
---|---|---|---|---|
Body weight (g) | 30.9 ± 1.6 | 30.2 ± 0.8 | 55.6 ± 2.7 † | 40.5 ± 4.8 ‡ |
Liver weight (g) | 1.6 ± 0.3 | 1.4 ± 0.1 | 3.4 ± 0.9 † | 2.0 ± 0.1 ** |
Epididymal wt (g) | 0.7 ± 0.2 | 0.4 ± 0.1 | 2.5 ± 0.3 † | 1.7 ± 0.2 ‡ |
Glucose (mg/dL) | 149.7 ± 37.9 | 137.3 ± 18.4 | 543.8 ± 34.1 † | 537.3 ± 25.0 † |
HbA1c (%) | 4.1 ± 0.1 | 3.9 ± 0.1 | 12.7 ± 1.1 † | 12.0 ± 0.6 † |
Insulin (ng/mL) | 0.36 ± 0.06 | 0.37 ± 0.14 | 4.75 ± 1.32 † | 1.81 ± 0.69 ‡ |
HOMAIR | 1.30 ± 0.40 | 1.42 ± 0.49 | 7.09 ± 2.31 † | 3.13 ± 0.86 ‡ |
Urinary 8-OH-dG (ng) | 30.8 ± 1.6 | 26.8 ± 7.7 | 224.5 ± 73.1 † | 42.0 ± 16.6 ‡ |
Urinary isoprostane (ng/24 h) | 4.2 ± 1.5 | 3.5 ± 0.6 | 44.5 ± 13.8 † | 18.5 ± 3.8 ‡ |
MCP-1 (pg/mL) | 141.5 ± 11.9 | 146.5 ± 18.6 | 343.1 ± 38.0 † | 187.9 ± 28.7 ‡ |
TNF-α (pg/mL) | 2.2 ± 0.3 | 2.1 ± 0.3 | 2.9 ± 0.4 † | 2.0 ± 0.2 ‡ |
ALT (U/L) | 23.7 ± 6.8 | 21.7 ± 2.8 | 52.2 ± 8.5 † | 31.5 ± 5.9 ‡ |
AST (U/L) | 27.5 ± 3.3 | 24.3 ± 6.9 | 49.2 ± 4.1 † | 32.2 ± 2.9 ‡ |
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Nam, H.; Lim, J.H.; Kim, T.W.; Kim, E.N.; Oum, S.-J.; Bae, S.H.; Park, C.W. Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation. Antioxidants 2023, 12, 2040. https://doi.org/10.3390/antiox12122040
Nam H, Lim JH, Kim TW, Kim EN, Oum S-J, Bae SH, Park CW. Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation. Antioxidants. 2023; 12(12):2040. https://doi.org/10.3390/antiox12122040
Chicago/Turabian StyleNam, Heechul, Ji Hee Lim, Tae Woo Kim, Eun Nim Kim, Sae-Jong Oum, Si Hyun Bae, and Cheol Whee Park. 2023. "Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation" Antioxidants 12, no. 12: 2040. https://doi.org/10.3390/antiox12122040