Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. PIP-2
2.3. Generation of CLP and Experimental Plan
2.4. Bacterial Culture
2.5. Biochemical Assays
2.6. Lung Histology
2.7. Statistical Analysis
3. Results
3.1. Tissue Uptake of PIP-2
3.2. Mortality
3.3. Bacterial Culture
3.4. Lung Histology
3.5. Lung MPO Activity and W/D
3.6. Lung Cytokines
3.7. Lung Oxidative Stress
4. Discussion
5. Conclusions
6. Patent Pending
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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PLA2 Activity nmol/h/mg Protein | ||||||||
---|---|---|---|---|---|---|---|---|
Mouse Organs | Lung | Kidney | Heart | Liver | ||||
2 h | 24 h | 2 h | 24 h | 2 h | 24 h | 2 h | 24 h | |
Liposomes | 8.21 ± 0.28 | ND | 6.61 ± 0.27 | ND | 4.75 ± 0.39 | ND | 5.32 ± 0.33 | ND |
Liposomes + PIP-2 (2 µg)/g | 1.49 ± 0.06 | 1.51 ± 0.09 | 1.25 ± 0.06 | 1.28 ± 0.04 | 0.95 ± 0.02 | 0.96 ± 0.06 | 1.26 ± 0.02 | 1.27 ± 0.09 |
Liposomes + PIP-2 (20 µg)/g | 1.44 ± 0.06 | ND | 1.09 ± 0.02 | ND | 0.85 ± 0.03 | ND | 1.22 ± 0.04 | ND |
Number of Mice | Mice Dead by 24 h | % Mortality | |
---|---|---|---|
CLP | 15 | 1 | 7 |
CLP + Antibiotics | 13 | 1 | 8 |
CLP + PIP-2 (2 µg/g) | 10 | 0 | 0 |
CLP + PIP – 2 (2µ/g) + Antibiotics | 11 | 1 | 9 |
CLP + PIP – 2 (10 µg/g) | 6 | 6 | 100 |
CLP + PIP – 2 (10 µg/g) + Antibiotics | 5 | 0 | 0 |
Colonies /mL of Lung Homogenate X 10−3 | Colonies /mL of Peritoneal Fluid X 10−3 | |||
---|---|---|---|---|
6 h | 24 h | 6 h | 24 h | |
Control | 0.32 ± 0.10 | 0.38 ± 0.80 | ||
CLP | 0.06 ± 0.05 | 68.4 ± 21.6 * | 10.5 ± 0.2 | 1522 ± 440 * |
CLP + PIP-2 (2 µg/g) | 0.09 ± 0.04 | 133 ± 16.5 ƚ | 15.8 ± 0.16 | 3894 ± 536 ƚ |
CLP + Antibiotics | 0 | 0.45 ± 0.14 | 0 | 0.30 ± 0.14 |
CLP + PIP – 2 (2 µg/g) + Antibiotics | 0 | 0.42 ± 0.16 | 0 | 0.32 ± 0.12 |
CLP + PIP – 2 (10 µg/g) + Antibiotics | 0 | 0.37 ± 0.09 | 0 | 0.34 + 0.11 |
MPO Activity nmol/mg Protein | Wet/Dry Weight | |||
---|---|---|---|---|
6 h | 24 h | 6 h | 24 h | |
Control | 4.94 ± 3.8 | 4.90 ± 0.14 | ||
CLP | 14.02 ± 7.3 | 68.7 ±9.8 * | 5.13 ± 0.26 | 7.32 ± 0.51 * |
CLP + PIP-2 (2 mg/g) | 0.66 ± 0.24 | 23.3 ± 6.6 * ƚ | 5.07 ± 0.23 | 6.24 ± 0.42 * ƚ |
CLP + Antibiotics | 0.29 ± 0.14 | 8.95 ± 4.1 ƚ | 5.00 ± 0.22 | 7.52 ± 0.16 * |
CLP + PIP - 2(2 µg/g) + Antibiotics | 0.04 ± 0.15 | 2.40 ± 6.5 ƚ | 5.01 ± 0.18 | 6.27 ± 0.47 * ƚ |
CLP + PIP - 2(10 µg/g) + Antibiotics | 0.26 ± 0.18 | 2.94 ± 1.6 ƚ | 5.02 ± 0.14 | 6.23 ± 0.21 * ƚ |
TBARS pmol/mg Prot. | 8-Isoprostanes pmol/mg Prot. | Protein Carbonyls nmol/mg Prot. | ||||
---|---|---|---|---|---|---|
6 h | 24 h | 6 h | 24 h | 6 h | 24 h | |
Control | 69.3 ± 2.6 | 32.3 ± 1.6 | 5.25 ± 0.40 | |||
CLP | 73.4 ± 5.9 | 243 ± 12 * | 32.9 ± 1.4 | 121 ± 5.8 * ƚ | 5.26 ± 0.02 | 16.1 ± 1.26 * |
CLP + PIP-2 (2 µg/g) | 72.8 ± 2.2 | 105 ± 5.5 * ƚ | 31.8 ± 4.8 | 59.6 ± 5.3 * ƚ | 5.31 ± 0.74 | 7.67 ± 0.23 * ƚ |
CLP + Antibiotics | 71.9 ± 2.8 | 231 ± 20 * | 32.1 ± 1.0 | 111 ± 9.4 * | 5.08 ± 0.33 | 15.8 ± 0.89 * |
CLP + PIP – 2 (2 µg/g) Antibiotics | 74.7 ± 5.6 | 108 ± 13 * ƚ | 33.7 ± 2.0 | 53.4 ± 6.3 * ƚ | 5.19 ± 0.33 | 7.74 ± 0.28 * ƚ |
CLP + PIP – 2 (10 µg/g) Antibiotics | 74 .5 ± 7.2 | 111 ± 2.6 * ƚ | 32.7 ± 1.8 | 56.6 ± 6.5 * ƚ | 4.96 ± 0.33 | 7.60 ± 0.15 * ƚ |
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Fisher, A.B.; Dodia, C.; Tao, J.-Q.; Feinstein, S.I.; Chatterjee, S. Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model. Antioxidants 2021, 10, 1676. https://doi.org/10.3390/antiox10111676
Fisher AB, Dodia C, Tao J-Q, Feinstein SI, Chatterjee S. Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model. Antioxidants. 2021; 10(11):1676. https://doi.org/10.3390/antiox10111676
Chicago/Turabian StyleFisher, Aron B., Chandra Dodia, Jian-Qin Tao, Sheldon I. Feinstein, and Shampa Chatterjee. 2021. "Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model" Antioxidants 10, no. 11: 1676. https://doi.org/10.3390/antiox10111676
APA StyleFisher, A. B., Dodia, C., Tao, J.-Q., Feinstein, S. I., & Chatterjee, S. (2021). Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model. Antioxidants, 10(11), 1676. https://doi.org/10.3390/antiox10111676