Involvement of Ferroptosis in Diabetes-Induced Liver Pathology
Abstract
:1. Introduction
2. Results
2.1. Fer-1 Attenuates Diabetes-Induced Liver Damage
2.2. Fer-1 Weakens Lipid Peroxidation in Diabetic Liver
2.3. Fer-1 Improves Diabetes-Induced Attenuation of GSH-Related Antioxidant Defense in the Liver
2.4. Fer-1 Re-Establishes Diabetes-Induced Disturbances in Hepatic Nrf2 Signaling
2.5. Fer-1 Abrogates Diabetes-Induced Activation of HMGB1 and Increase in Inflammatory Cytokines
3. Discussion
4. Materials and Methods
4.1. Experimental Design
4.2. Biochemical Serum Analysis
4.3. Microscopic Examination
4.3.1. Histological, Morphometric, and Stereological Analyses
4.3.2. Iron Staining
4.3.3. Lipofuscin Detection
4.3.4. Immunohistochemistry
4.4. Analysis of GSH Content and Activities of Antioxidative Defense Enzymes
4.5. SDS-Polyacrylamide Gel Electrophoresis (PAGE) and Western Blot Analysis
4.6. ELISA Assay for Measurement of TNF-α and IL-6
4.7. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ctrl | DM | DM + Fer-1 | ANOVA | |
---|---|---|---|---|
Body mass (g) | 26.8 ± 0.9 | 23.0 ± 0.8 * | 23.3 ± 1.4 | F(2) = 4.17 p = 0.0300 |
Blood glucose (mmol/L) | 9.0 ± 0.4 | 16.8 ± 1.7 ** | 13.9 ± 1.5 | F(2) = 7.34 p = 0.0043 |
Serum ALT (U/L) | 57.2 ± 5.6 | 76.2 ± 2.5 * | 61.1 ± 5.2 # | F(2) = 4.08 p = 0.0472 |
Serum TG (mmol/L) | 1.548 ± 0.02 | 1.7 ± 0.05 * | 1.5 ± 0.05 # | F(2) = 7.78 p = 0.0068 |
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Stancic, A.; Velickovic, K.; Markelic, M.; Grigorov, I.; Saksida, T.; Savic, N.; Vucetic, M.; Martinovic, V.; Ivanovic, A.; Otasevic, V. Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. Int. J. Mol. Sci. 2022, 23, 9309. https://doi.org/10.3390/ijms23169309
Stancic A, Velickovic K, Markelic M, Grigorov I, Saksida T, Savic N, Vucetic M, Martinovic V, Ivanovic A, Otasevic V. Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. International Journal of Molecular Sciences. 2022; 23(16):9309. https://doi.org/10.3390/ijms23169309
Chicago/Turabian StyleStancic, Ana, Ksenija Velickovic, Milica Markelic, Ilijana Grigorov, Tamara Saksida, Nevena Savic, Milica Vucetic, Vesna Martinovic, Andjelija Ivanovic, and Vesna Otasevic. 2022. "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology" International Journal of Molecular Sciences 23, no. 16: 9309. https://doi.org/10.3390/ijms23169309