Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Animals and Experimental Design
2.3. Post Mitochondrial Supernatant Preparation
2.4. Estimation of Serum Enzyme Activities
2.4.1. Estimation of Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferases (ALT)
2.4.2. Assay for Lactate Dehydrogenase Activity
2.4.3. Estimation of Protein
2.4.4. Estimation of Alkaline Phosphatase (ALP)
2.5. Measurement of ROS
2.6. Estimation of Lipid Peroxidation
2.7. Estimation of Antioxidant Enzyme Armory
2.7.1. Assay for Superoxide Dismutase Activity (SOD)
2.7.2. Catalase Activity
2.7.3. Estimation of Glutathione (GSH)
2.7.4. Glutathione Reductase (GR) Activity
2.7.5. Glutathione Peroxidase Activity
2.8. Measurement of Nitric Oxide (NO)
2.9. Assay for Hydrogen Peroxide (H2O2)
2.10. Histopathological Examination
2.11. Immunostaining
2.12. Inflammatory Mediators
2.13. Ethical Statement
2.14. Statistical Analysis
3. Results
3.1. Effect of Naringenin Treatment on the ROS Levels
3.2. Effect of Naringenin Treatment on the Antioxidant Enzyme System
3.3. Effect of Naringenin Treatment on H2O2 Levels
3.4. Effect of Naringenin Treatment on MDA Levels
3.5. Naringenin Treatment Alleviates Serum Toxicity Parameters in Dox-Induced Liver Toxicity
3.6. Effect of Naringenin and Dox Treatment on NF-κB and Other Inflammatory Mediators
3.7. Effect of Naringenin on NO Production
3.8. Effect of Naringenin on Liver Histology
3.9. Effect of Naringenin on Expression of COX-2
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Groups | Treatment |
---|---|
Group I | Animals received normal diet for 20 consecutive days. |
Group II | A single intraperitoneal injection of Dox at the dose of 20 mg/kg body weight on 20th day along with normal diet for 20 consecutive days. |
Group III | Animals were first treated with normal diet and naringenin (50 mg/kg body weight) for 20 days before the Dox treatment (as in group II). |
Group IV | Animals were first treated with normal diet and naringenin (100 mg/kg body weight) for 20 days before the Dox treatment (as in group II). |
Group I | Group II | Group III | Group IV | |
---|---|---|---|---|
Reduced Glutathione (GSH; nmol mg protein) | 333.10 ± 15.1 | 146.12 ± 16.2 *** | 192.32 ± 13.4 # | 307.42 ± 29.7 ### |
Oxidized Glutathione (GSSG; nmol mg protein) | 43.42 ± 3.02 | 89.32 ± 7.71 *** | 64.34 ± 5.32 # | 46.03 ± 3.38 ### |
GPx (nmol/min/mg protein) | 190.39 ± 19.3 | 79.15 ± 7.07 *** | 147.33 ± 12.1 ## | 159.65 ± 11.2 ## |
GR (nmol min/min/mg protein) | 227.61 ± 19.6 | 101.31 ± 10.5 *** | 165.09 ± 13.5 ## | 210.20 ± 22.8 ### |
SOD (units/min/mg protein) | 14.93 ± 2.87 | 4.83 ± 0.71 *** | 8.53 ± 0.82 # | 10.14 ± 1.32 ### |
Catalase (nmol H2O2 consumed/min/mg protein) | 9.41 ± 0.81 | 2.01 ± 0.11 *** | 5.82 ± 0.51 ### | 7.32 ± 0.64###b |
H2O2 (nmol of H2O2 /g tissue) | 192.1 ± 18.7 | 407.3 ± 19.2 *** | 333.2 ± 26.1 # | 212.1 ± 19.5 ### |
Treatment Regimen | ALT (IU/L) | AST (IU/L) | ALP (IU/L) | Total Protein (IU/L) | LDH (nmol NADH oxidized/min/mg Protein) |
---|---|---|---|---|---|
Group I | 67.73 ± 4.12 | 108.3 ± 9.9 | 103. 4± 9.11 | 6.01 ± 0.49 | 112.91 ± 15.3 |
Group II | 119.4 ± 6.42 *** | 300.6 ± 14.9 *** | 201.3 ± 8.20 *** | 3.13 ± 0.19 *** | 302.23 ± 19.7 *** |
Group III | 99.21 ± 7.92 # | 210.2 ± 16.5 # | 172.2 ± 9.32 # | 3.87 ± 0.22 ns | 198.76 ± 25.9 # |
Group IV | 80.31 ± 4.64 ## | 151.1 ± 7.83 ### | 115.9 ± 10.8 ### | 5.01 ± 0.49 ## | 151.03 ± 15.9 ## |
Group I | Group II | Group III | Group IV | |
---|---|---|---|---|
NFκ-B (pg/mL) | 901.62 ± 71.6 | 2341.10 ± 61.5 *** | 1952.32 ± 38.2 # | 1102.32 ± 31.7 ### |
TNF-α (pg/mL) | 247.30 ± 17.8 | 552.18 ± 27.2 *** | 321.01 ± 14.0 ## | 269.11 ± 19.2 ### |
IL-1β (pg/mL) | 892.90 ± 41.4 | 1746.18 ± 61.0 *** | 1485.44 ± 70.1 # | 901.14 ± 38.3 ### |
IL-6 (pg/mL) | 975.15 ± 80.2 | 2127.83 ± 57.1 *** | 1763.20 ± 44.1 # | 1001.62 ± 67.7 ### |
TGF-β (pg/mL) | 259.18 ± 13.8 | 722.95 ± 42.1 *** | 431.38 ± 21.4 ## | 271.83 ± 31.8 ### |
PGE-2 (pg/mL) | 139.97 ± 14.4 | 527.36 ± 32.0 *** | 154.11 ± 13.2 ### | 146.02 ± 13.0 ### |
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Wali, A.F.; Rashid, S.; Rashid, S.M.; Ansari, M.A.; Khan, M.R.; Haq, N.; Alhareth, D.Y.; Ahmad, A.; Rehman, M.U. Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation. Plants 2020, 9, 550. https://doi.org/10.3390/plants9040550
Wali AF, Rashid S, Rashid SM, Ansari MA, Khan MR, Haq N, Alhareth DY, Ahmad A, Rehman MU. Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation. Plants. 2020; 9(4):550. https://doi.org/10.3390/plants9040550
Chicago/Turabian StyleWali, Adil Farooq, Summya Rashid, Shahzada Mudasir Rashid, Mushtaq Ahmad Ansari, Mohammad Rashid Khan, Nazrul Haq, Dhafer Yahya Alhareth, Ajaz Ahmad, and Muneeb U. Rehman. 2020. "Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation" Plants 9, no. 4: 550. https://doi.org/10.3390/plants9040550