Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
Abstract
:1. Introduction
2. Results
2.1. Body and Organ Weights
2.2. Histopathological Evaluation
2.3. Serum Chemistry Analysis
2.4. BAL Total and Differential Cell Counts
2.5. Changes in Cytokine Levels in BAL, the Lungs, and the Liver
2.6. Measurement of HMGB1 and sPLA2 in BAL Fluid
2.7. Measurement of mRNA and Protein Expression Levels in the Liver and Lung Tissues
2.8. Zebrafish Assay
2.9. PHMG-P Induced Cytotoxicity at Various Serum Concentrations
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Animal Experiment
4.3. Bronchoalveolar Lavage
4.4. Histopathological Examination
4.5. Serum Chemistry
4.6. Cytokine Measurement in BAL Fluid, the Lungs, and the Liver
4.7. Quantitative Real-Time PCR
4.8. Western Blot Analysis
4.9. Cell Culture
4.10. Zebrafish Assay
4.11. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Day | Control | 0.9 mg/kg IV | 7.2 mg/kg IV | 0.9 mg/kg ITI |
---|---|---|---|---|
−3 | 21.80 ± 0.75 a | 22.04 ± 0.63 | 21.95 ± 0.80 | 21.80 ± 0.68 |
1 | 22.68 ± 0.86 | 23.19 ± 0.76 | 20.32 ± 1.12 ** | 19.49 ± 0.71 ** |
2 | 22.02 ± 0.85 | 22.48 ± 0.71 | 19.87 ± 1.17 ** | 17.36 ± 0.65 ** |
4 | 22.71 ± 0.90 | 23.53 ± 0.80 | 20.16 ± 1.29 ** | 17.07 ± 0.78 ** |
7 | 23.04 ± 0.97 | 24.13 ± 0.83 | 20.66 ± 0.97 ** | 18.64 ± 1.60 ** |
4 h | Control | 0.9 mg/kg IV | 7.2 mg/kg IV | 0.9 mg/kg ITI |
---|---|---|---|---|
BUN a (mg/dL) | 22.80 ± 1.74 | 20.30 ± 2.82 | 26.30 ± 3.11 * | 23.20 ± 1.67 |
CREA (mg/dL) | 0.28 ± 0.04 | 0.29 ± 0.02 | 0.29 ± 0.03 | 0.23 ± 0.02 * |
TP (g/dL) | 5.11 ± 0.18 | 4.87 ± 0.22 | 5.85 ± 0.28 ** | 5.54 ± 0.38 * |
ALB (g/dL) | 3.31 ± 0.11 | 3.15 ± 0.19 | 3.67 ± 0.16 ** | 3.52 ± 0.19 * |
AST (IU/L) | 55.60 ± 15.73 | 55.20 ± 4.77 | 92.10 ± 8.20 ** | 108.90 ± 31.72 ** |
ALT (IU/L) | 28.80 ± 5.30 | 29.20 ± 3.7 | 45.20 ± 11.35 * | 62.70 ± 34.23 |
GGT (IU/L) | 1.85 ± 0.27 | 1.82 ± 0.35 | 2.06 ± 0.37 | 2.09 ± 0.59 |
ALP (IU/L) | 485.10 ± 36.46 | 491.90 ± 39.36 | 541.50 ± 45.88 * | 483.90 ± 49.16 |
TCHO (mg/dL) | 84.10 ± 4.59 | 82.90 ± 5.99 | 98.10 ± 7.82** | 88.80 ± 5.36 |
TG (mg/dL) | 46.00 ± 7.12 | 66.80 ± 20.17 | 164.70 ± 94.69 * | 77.70 ± 13.22 ** |
D1 | Control | 0.9 mg/kg IV | 7.2 mg/kg IV | 0.9 mg/kg ITI |
BUN (mg/dL) | 27.20 ± 3.98 | 28.60 ± 4.30 | 20.20 ± 2.68 ** | 21.50 ± 2.46 * |
CREA (mg/dL) | 0.33 ± 0.04 | 0.34 ± 0.04 | 0.30 ± 0.03 | 0.28 ± 0.02 |
TP (g/dL) | 5.34 ± 0.33 | 5.30 ± 0.30 | 5.60 ± 0.25 | 5.51 ± 0.30 |
ALB (g/dL) | 3.45 ± 0.16 | 3.42 ± 0.12 | 3.63 ± 0.19 | 3.59 ± 0.16 |
AST (IU/L) | 48.20 ± 6.31 | 45.40 ± 4.13 | 53.8 ± 5.94 | 52.7 ± 4.79 |
ALT (IU/L) | 28.10 ± 4.39 | 28.90 ± 3.43 | 23.30 ± 1.45 * | 23.10 ± 3.50 * |
GGT (IU/L) | 1.96 ± 0.14 | 1.93 ± 0.40 | 2.08 ± 0.29 | 1.92 ± 0.34 |
ALP (IU/L) | 485.30 ± 57.82 | 534.80 ± 51.46 | 457.60 ± 52.09 | 480.80 ± 51.26 |
TCHO (mg/dL) | 85.40 ± 4.90 | 88.60 ± 5.39 | 101.60 ± 9.48 ** | 95.80 ± 4.76 ** |
TG (mg/dL) | 66.50 ± 15.83 | 64.80 ± 13.22 | 46.50 ± 10.52 * | 57.00 ± 19.31 |
D7 | Control | 0.9 mg/kg IV | 7.2 mg/kg IV | 0.9 mg/kg ITI |
BUN (mg/dL) | 30.00 ± 4.13 | 29.80 ± 3.66 | 35.30 ± 6.82 | 30.30 ± 4.24 |
CREA (mg/dL) | 0.31 ± 0.04 | 0.31 ± 0.03 | 0.32 ± 0.03 | 0.29 ± 0.03 |
TP (g/dL) | 5.53 ± 0.15 | 5.59 ± 0.29 | 5.51 ± 0.30 | 5.51 ± 0.34 |
ALB (g/dL) | 3.41 ± 0.09 | 3.39 ± 0.15 | 3.47 ± 0.18 | 3.49 ± 0.18 |
AST (IU/L) | 48.20 ± 2.77 | 47.40 ± 4.58 | 57.40 ± 6.51 * | 61.30 ± 10.44 ** |
ALT (IU/L) | 31.10 ± 1.78 | 32.00 ± 5.33 | 31.60 ± 3.60 | 38.60 ± 8.29 |
GGT (IU/L) | 1.66 ± 0.32 | 1.77 ± 0.21 | 1.91 ± 0.32 | 1.78 ± 0.19 |
ALP (IU/L) | 426.90 ± 51.04 | 450.80 ± 49.71 | 405.80 ± 30.36 | 376.90 ± 40.01 |
TCHO (mg/dL) | 84.89 ± 7.72 | 83.22 ± 6.40 | 93.33 ± 6.89 | 96.11 ± 8.59 * |
TG (mg/dL) | 94.47 ± 24.30 | 72.33 ± 12.31 | 90.33 ± 31.97 | 80.58 ± 22.88 |
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Song, J.; Jung, K.-J.; Yang, M.-J.; Kim, W.; Lee, B.-S.; Choe, S.-K.; Kim, S.-J.; Hwang, J.-H. Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure. Int. J. Mol. Sci. 2022, 23, 3289. https://doi.org/10.3390/ijms23063289
Song J, Jung K-J, Yang M-J, Kim W, Lee B-S, Choe S-K, Kim S-J, Hwang J-H. Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure. International Journal of Molecular Sciences. 2022; 23(6):3289. https://doi.org/10.3390/ijms23063289
Chicago/Turabian StyleSong, Jeongah, Kyung-Jin Jung, Mi-Jin Yang, Woojin Kim, Byoung-Seok Lee, Seong-Kyu Choe, Seong-Jin Kim, and Jeong-Ho Hwang. 2022. "Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure" International Journal of Molecular Sciences 23, no. 6: 3289. https://doi.org/10.3390/ijms23063289