Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation
Abstract
:1. Introduction
2. Results
2.1. Characterization of PAA
2.2. Relative Lung Weights
2.3. Cell Analysis and Lactate Dehydrogenase (LDH) Activity in Bronchoalveolar Lavage Fluid (BALF)
2.4. Concentration of Cytokine-Induced Neutrophil Chemoattractants (CINC) in BALF and Concentration of Heme Oxygenase (HO)-1 in Lung Tissue
2.5. Micro-CT Imaging
2.6. Histopathological Features in the Lung
3. Discussion
4. Materials and Methods
4.1. Sample Polymers
4.2. Animals
4.3. Intratracheal Instillation
4.4. Animals Following Intratracheal Instillation
4.5. Cytospin Analysis of Inflammatory Cells and Measurement of LDH in BALF
4.6. Measurement of Chemokines in BALF and HO-1 in Lung Tissue
4.7. 3D Micro-CT Imaging
4.8. Histopathology
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
(A) HMW | |||||||||||
Observation Point | Group | Ashcroft Score | vs. 3 Days | vs. 1 Week | vs. 1 Month | ||||||
Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | |||
3 days | Control | 0.0 ± 0.0 | - | N.S. | N.S. | N.S. | p < 0.01 | p < 0.01 | N.S. | N.S. | p < 0.01 |
0.2 mg | 0.5 ± 0.2 | N.S. | - | N.S. | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |
1.0 mg | 0.7 ± 0.2 | N.S. | N.S. | - | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |
1 week | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | - | p < 0.01 | p < 0.01 | N.S. | N.S. | p < 0.01 |
0.2 mg | 1.0 ± 0.5 | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | p < 0.01 | N.S. | p < 0.01 | |
1.0 mg | 3.4 ± 0.9 | N.S. | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | p < 0.01 | ||
1 month | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | N.S. | p < 0.01 |
0.2 mg | 0.6 ± 0.1 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | |
1.0 mg | 3.1 ± 0.4 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | |
3 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. |
0.2 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
1.0 mg | 2.5 ± 0.4 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
6 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. |
0.2 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
1.0 mg | 2.0 ± 0.8 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
(A) HMW | |||||||||||
Observation Point | Group | Ashcroft Score | vs. 3 Months | vs. 6 Months | |||||||
Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | ||||||
3 days | Control | 0.0 ± 0.0 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |||
0.2 mg | 0.5 ± 0.2 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | ||||
1.0 mg | 0.7 ± 0.2 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | ||||
1 week | Control | 0.0 ± 0.0 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |||
0.2 mg | 1.0 ± 0.5 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | ||||
1.0 mg | 3.4 ± 0.9 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | ||||
1 month | Control | 0.0 ± 0.0 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |||
0.2 mg | 0.6 ± 0.1 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | ||||
1.0 mg | 3.1 ± 0.4 | p < 0.01 | p < 0.01 | N.S. | p < 0.01 | p < 0.01 | p < 0.01 | ||||
3 months | Control | 0.0 ± 0.0 | - | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | |||
0.2 mg | 0.1 ± 0.1 | N.S. | - | p < 0.01 | N.S. | N.S. | p < 0.01 | ||||
1.0 mg | 2.5 ± 0.4 | N.S. | N.S. | - | p < 0.01 | p < 0.01 | N.S. | ||||
6 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | - | N.S. | p < 0.01 | |||
0.2 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | ||||
1.0 mg | 2.0 ± 0.8 | N.S. | N.S. | N.S. | N.S. | N.S. | - | ||||
(B) LMW | |||||||||||
Observation Point | Group | Ashcroft Score | vs. 3 Days | vs. 1 Week | vs. 1 Month | ||||||
Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | |||
3 days | Control | 0.0 ± 0.0 | - | N.S. | p < 0.01 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | N.S. |
0.2 mg | 0.0 ± 0.1 | N.S. | - | p < 0.01 | N.S. | N.S. | p < 0.01 | N.S. | N.S. | N.S. | |
1.0 mg | 0.5 ± 0.2 | N.S. | N.S. | - | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | |
1 week | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | - | N.S. | p < 0.01 | N.S. | N.S. | N.S. |
0.2 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | N.S. | p < 0.01 | N.S. | |
1.0 mg | 0.4 ± 0.2 | N.S. | N.S. | N.S. | N.S. | N.S. | - | p < 0.01 | p < 0.01 | p < 0.01 | |
1 month | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | N.S. | N.S. |
0.2 mg | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | N.S. | |
1.0 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | - | |
3 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. |
0.2 mg | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
1.0 mg | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
6 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. |
0.2 mg | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
1.0 mg | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |
(B) LMW | |||||||||||
Observation Point | Group | Ashcroft Score | vs. 3 Months | vs. 6 Months | |||||||
Control | 0.2 mg | 1.0 mg | Control | 0.2 mg | 1.0 mg | ||||||
3 days | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |||
0.2 mg | 0.5 ± 0.2 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | ||||
1.0 mg | 0.7 ± 0.2 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | ||||
1 week | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |||
0.2 mg | 1.0 ± 0.5 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | ||||
1.0 mg | 3.4 ± 0.9 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | ||||
1 month | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | |||
0.2 mg | 0.6 ± 0.1 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | ||||
1.0 mg | 3.1 ± 0.4 | N.S. | N.S. | N.S. | N.S. | N.S. | N.S. | ||||
3 months | Control | 0.0 ± 0.0 | - | N.S. | N.S. | N.S. | N.S. | N.S. | |||
0.2 mg | 0.1 ± 0.1 | N.S. | - | N.S. | N.S. | N.S. | N.S. | ||||
1.0 mg | 2.5 ± 0.4 | N.S. | N.S. | - | N.S. | N.S. | N.S. | ||||
6 months | Control | 0.0 ± 0.0 | N.S. | N.S. | N.S. | - | N.S. | N.S. | |||
0.2 mg | 0.1 ± 0.1 | N.S. | N.S. | N.S. | N.S. | - | N.S. | ||||
1.0 mg | 2.0 ± 0.8 | N.S. | N.S. | N.S. | N.S. | N.S. | - |
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Name | Polyacrylic Acid | Structural Formula | ||
---|---|---|---|---|
CAS number | 9003-01-4 | |||
High molecular weight | Low molecular weight | |||
Bulk | Purity | ≦100% | ≦100% | |
Weight average molecular weight (MW) | 598,000 g/mol | 30,900 g/mol | ||
Number average molecular weight (Mn) | 451,000 g/mol | 25,800 g/mol | ||
Poly dispersity index (PDI) | 1.33 | 1.20 | ||
Cross-linking | None | None | ||
Appearance | Solid, white powdered | Solid, white powdered | ||
Odor | None | None | ||
Secondary diameter | 2.83 µm | 269 nm | ||
Suspension | Radius of gyration (Rg) | 57.5 nm | 13.5 nm | |
Hydrodynamic radius (Rh) | 39.7 nm (Molecular dispersion) | 2.78 nm (Molecular dispersion) | ||
217 nm (H2O dispersion: Suspension for instillation) | 1.11 nm (H2O dispersion: Suspension for instillation) | |||
Secondary diameter | 39.3 nm | 53.2 nm |
3 Days | 1 Week | 1 Month | 3 Months | 6 Months | ||
---|---|---|---|---|---|---|
Relative lung weight (% ± SD) | ||||||
Control (distilled water) | 0.36 ± 0.03 | 0.34 ± 0.01 | 0.32 ± 0.01 | 0.32 ± 0.01 | 0.32 ± 0.01 | |
HMW | 0.2 mg | 0.50 ± 0.03 ** | 0.48 ± 0.02 ** | 0.38 ± 0.01 ** | 0.33 ± 0.01 | 0.32 ± 0.01 |
HMW | 1.0 mg | 0.73 ± 0.03 ** | 0.70 ± 0.05 ** | 0.50 ± 0.01 ** | 0.43 ± 0.02 ** | 0.39 ± 0.02 ** |
Control (distilled water) | 0.37 ± 0.01 | 0.35 ± 0.03 | 0.33 ± 0.02 | 0.30 ± 0.01 | 0.30 ± 0.03 | |
LMW | 0.2 mg | 0.42 ± 0.02 ** | 0.38 ± 0.02 | 0.34 ± 0.01 | 0.31 ± 0.01 | 0.30 ± 0.01 |
LMW | 1.0 mg | 0.54 ± 0.02 ** | 0.48 ± 0.02 ** | 0.39 ± 0.02 ** | 0.31 ± 0.01 * | 0.30 ± 0.01 |
3 Days | 1 Week | 1 Month | 3 Months | 6 Months | ||
---|---|---|---|---|---|---|
Total cell count (×1000 cells/mL ± SD) | ||||||
Control (distilled water) | 122.4 ± 36.3 | 137.5 ± 21.8 | 98.4 ± 34.5 | 185.0 ± 64.5 | 174.8 ± 59.0 | |
HMW | 0.2 mg | 580.0 ± 228.9 ** | 449.4 ± 42.5 * | 403.7 ± 42.3 ** | 191.7 ± 29.6 | 212.3 ± 74.3 |
HMW | 1.0 mg | 1043.6 ± 165.3 ** | 592.3 ± 189.0 ** | 407.3 ± 154.6 ** | 166.0 ± 53.2 | 186.5 ± 34.2 |
Control (distilled water) | 94.5 ± 9.9 | 69.3 ± 14.5 | 80.4 ± 28.4 | 75.2 ± 19.6 | 89.4 ± 28.2 | |
LMW | 0.2 mg | 342.2 ± 98.5 ** | 147.1 ± 27.9 | 88.8 ± 39.0 | 91.2 ± 15.3 | 102.9 ± 30.1 |
LMW | 1.0 mg | 1021.1 ± 116.9 ** | 606.0 ± 235.8 ** | 61.4 ± 15.3 | 59.4 ± 17.7 | 96.8 ± 21.4 |
Macrophage count (×1000 cells/mL ± SD) | ||||||
Control (distilled water) | 121.6 ± 34.8 | 137.2 ± 21.8 | 97.4 ± 34.1 | 183.8 ± 63.5 | 172.4 ± 57.6 | |
HMW | 0.2 mg | 215.5 ± 92.9 | 272.2 ± 41.9 * | 359.9 ± 37.7 ** | 190.4 ± 29.4 | 210.6 ± 72.3 |
HMW | 1.0 mg | 411.7 ± 73.1 ** | 379.3 ± 114.5 ** | 395.0 ± 158.0 ** | 164.9 ± 53.3 | 182.6 ± 32.2 |
Control (distilled water) | 93.0 ± 9.1 | 69.1 ± 14.6 | 79.6 ± 27.8 | 73.9 ± 19.4 | 87.9 ± 28.3 | |
LMW | 0.2 mg | 168.1 ± 29.2 ** | 128.4 ± 22.1 | 87.9 ± 38.6 | 90.2 ± 15.3 | 102.2 ± 29.2 |
LMW | 1.0 mg | 255.5 ± 28.5 ** | 323.0 ± 137.8 ** | 60.6 ± 15.2 | 57.8 ± 16.7 | 95.5 ± 21.3 |
Neutrophil count (×1000 cells/mL ± SD) | ||||||
Control (distilled water) | 1.7 ± 2.1 | 0.3 ± 0.4 | 0.4 ± 0.6 | 1.1 ± 1.3 | 1.9 ± 2.0 | |
HMW | 0.2 mg | 352.2 ± 137.1 ** | 169.2 ± 27.2 ** | 33.5 ± 18.7 ** | 1.1 ± 0.8 | 1.4 ± 1.9 |
HMW | 1.0 mg | 606.1 ± 141.4 ** | 197.4 ± 83.0 ** | 5.1 ± 3.3 | 0.8 ± 0.6 | 3.9 ± 2.6 |
Control (distilled water) | 0.7 ± 0.6 | 0.1 ± 0.1 | 0.5 ± 0.6 | 0.8 ± 0.8 | 0.9 ± 1.2 | |
LMW | 0.2 mg | 171.1 ± 76.3 ** | 17.0 ± 9.2 | 0.4 ± 0.6 | 0.6 ± 0.8 | 0.4 ± 0.7 |
LMW | 1.0 mg | 739.7 ± 81.4 ** | 251.5 ± 93.4 ** | 0.7 ± 0.3 | 1.5 ± 1.2 | 0.2 ± 0.4 |
Percentage of neutrophil (% ± SD) | ||||||
Control (distilled water) | 1.1 ± 1.3 | 0.2 ± 0.3 | 0.5 ± 0.7 | 0.5 ± 0.5 | 1.0 ± 0.7 | |
HMW | 0.2 mg | 60.8 ± 4.4 ** | 37.8 ± 5.9 ** | 8.3 ± 4.5 ** | 0.6 ± 0.4 | 0.5 ± 0.7 |
HMW | 1.0 mg | 57.8 ± 6.3 ** | 32.8 ± 7.1 ** | 1.5 ± 1.3 | 0.5 ± 0.4 | 2.0 ± 1.2 |
Control (distilled water) | 0.7 ± 0.6 | 0.1 ± 0.2 | 0.5 ± 0.5 | 1.0 ± 0.9 | 1.1 ± 1.4 | |
LMW | 0.2 mg | 48.2 ± 8.7 ** | 11.1 ± 5.5 ** | 0.4 ± 0.4 | 0.7 ± 0.8 | 0.3 ± 0.4 |
LMW | 1.0 mg | 72.5 ± 2.2 ** | 41.6 ± 6.7 ** | 1.1 ± 0.5 | 2.2 ± 1.3 | 0.2 ± 0.4 |
Lymphocyte count (×1000 cells/mL ± SD) | ||||||
Control (distilled water) | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.6 ± 0.9 | 0.1 ± 0.3 | 0.4 ± 0.8 | |
HMW | 0.2 mg | 1.6 ± 3.7 | 0.4 ± 0.8 | 9.9 ± 6.7 * | 0.0 ± 0.0 | 0.3 ± 0.7 |
HMW | 1.0 mg | 7.0 ± 7.6 | 3.1 ± 2.6 * | 7.1 ± 5.0 | 0.3 ± 0.4 | 0.0 ± 0.0 |
Control (distilled water) | 0.7 ± 0.8 | 0.1 ± 0.2 | 0.3 ± 0.4 | 0.5 ± 0.5 | 0.5 ± 0.2 | |
LMW | 0.2 mg | 2.3 ± 2.0 | 0.5 ± 0.7 | 0.4 ± 0.4 | 0.4 ± 0.4 | 0.3 ± 0.3 |
LMW | 1.0 mg | 10.8 ± 11.2 | 14.6 ± 12.2 * | 0.1 ± 0.1 | 0.1 ± 0.1 | 1.0 ± 0.3 |
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Nishida, C.; Izumi, H.; Tomonaga, T.; Wang, K.-Y.; Higashi, H.; Takeshita, J.-I.; Ono, R.; Sumiya, K.; Fujii, S.; Hata, Y.; Sakurai, K.; Higashi, Y.; Yamasaki, K.; Yatera, K.; Morimoto, Y. Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation. Int. J. Mol. Sci. 2022, 23, 10345. https://doi.org/10.3390/ijms231810345
Nishida C, Izumi H, Tomonaga T, Wang K-Y, Higashi H, Takeshita J-I, Ono R, Sumiya K, Fujii S, Hata Y, Sakurai K, Higashi Y, Yamasaki K, Yatera K, Morimoto Y. Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation. International Journal of Molecular Sciences. 2022; 23(18):10345. https://doi.org/10.3390/ijms231810345
Chicago/Turabian StyleNishida, Chinatsu, Hiroto Izumi, Taisuke Tomonaga, Ke-Yong Wang, Hidenori Higashi, Jun-Ichi Takeshita, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Yuki Hata, Kazuo Sakurai, Yasuyuki Higashi, Kei Yamasaki, Kazuhiro Yatera, and Yasuo Morimoto. 2022. "Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation" International Journal of Molecular Sciences 23, no. 18: 10345. https://doi.org/10.3390/ijms231810345