Interaction between ZnO Nanoparticles and Albumin and Its Effect on Cytotoxicity, Cellular Uptake, Intestinal Transport, Toxicokinetics, and Acute Oral Toxicity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials and NP Preparation
2.2. Characterization
2.3. Dissolution Properties of ZnO NPs
2.4. ICP–AES Analysis
2.5. Fluorescence Quenching of Food Proteins by ZnO NPs
2.6. SDS–Polyacrylamide Gel Electrophoresis (PAGE) Analysis
2.7. Cytotoxicity
2.7.1. Cell Culture
2.7.2. Cell Proliferation
2.7.3. Lactate Dehydrogenase Leakage (LDH) Assay
2.7.4. Reactive Oxygen Species (ROS) Generation
2.8. Cellular Uptake
2.9. Intestinal Transport
2.10. Animals
2.11. Toxicokinetic Study
2.12. 14-Day Repeated Oral Toxicity Study
2.13. Statistical Analysis
3. Results and Discussion
3.1. Characterization of ZnO NPs in Food Proteins
3.2. Solubility of ZnO NPs in Food Proteins
3.3. Interactions between ZnO NPs and Food Proteins
3.4. Primary Structural Stability and Digestion of Food Proteins by Interactions with ZnO NPs
3.5. Cytotoxicity of ZnO NPs by Interactions with Food Proteins
3.6. Cellular Uptake of ZnO NPs by Interactions with Food Proteins
3.7. Intestinal Transport of ZnO NPs by Interactions with Food Proteins
3.8. Toxicokinetics of ZnO NPs by Interactions with Food Matrices
3.9. Oral Toxicity of ZnO NPs by Interactions with Food Matrices
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Toxicokinetic Parameters | DW | 5% Albumin | 5% Glucose |
---|---|---|---|
Cmax (µg/mL) | 25.3 ± 3.1 a | 25.3 ± 2.1 a | 41.9 ± 4.6 b |
Tmax (h) | 1.3 ± 0.5 a | 1.0 ± 0.0 a | 3.5 ± 1.0 b |
AUC (h × µg/mL) | 132.8 ± 27.1 a | 126.5 ± 18.2 a | 280.9 ± 49.8 b |
T1/2 (h) | 2.5 ± 0.0 a | 2.7 ± 0.2 a | 4.5 ± 0.4 b |
MRT (h) | 4.0 ± 0.4 a | 4.3 ± 0.2 a | 5.8 ± 0.7 b |
CL/F (mL/h) | 625.2 ± 151.1 a | 641.1 ± 82.3 a | 256.6 ± 24.0 b |
Absorption (%) | 8.9 ± 1.9 a | 8.4 ± 0.3 a | 18.8 ± 3.1 b |
Organ | Control | DW | 5% Albumin | 5% Glucose |
---|---|---|---|---|
Brain | 0.8 ± 0.0 | 0.8 ± 0.1 | 0.8 ± 0.1 | 0.8 ± 0.1 |
Heart | 0.4 ± 0.0 | 0.4 ± 0.0 | 0.4 ± 0.0 | 0.4 ± 0.0 |
Kidney | 0.8 ± 0.1 | 0.8 ± 0.0 | 0.8 ± 0.1 | 0.8 ± 0.0 |
Large intestine | 1.9 ± 0.3 | 1.6 ± 0.3 | 1.7 ± 0.3 | 1.5 ± 0.6 |
Liver | 3.7 ± 0.2 | 3.8 ± 0.3 | 3.9 ± 0.3 | 3.9 ± 0.2 |
Lung | 0.6 ± 0.1 | 0.6 ± 0.1 | 0.6 ± 0.1 | 0.6 ± 0.1 |
Ovary | 0.1 ± 0.0 | 0.1 ± 0.0 | 0.1 ± 0.0 | 0.1 ± 0.0 |
Small intestine | 4.1 ± 0.4 | 4.2 ± 0.3 | 4.3 ± 0.3 | 4.1 ± 0.3 |
Spleen | 0.3 ± 0.1 | 0.3 ± 0.0 | 0.3 ± 0.0 | 0.3 ± 0.1 |
Stomach | 1.7 ± 0.3 | 1.7 ± 0.6 | 1.5 ± 0.4 | 1.3 ± 0.3 |
Groups | WBC | WBC Differential Counting (%) | RBC | Hb | HCT | MCV | MCH | MCHC | RETI | PLT | PT | APTT | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(103/μL) | NE | LY | MO | EO | BA | (106/μL) | (g/dL) | (%) | (fL) | (pg) | (g/dL) | (%) | (103/μL) | (s) | (s) | |
Control | 6.89 ± 0.86 | 10.3 ± 1.9 | 85.0 ± 1.9 | 1.9 ± 0.3 | 1.3 ± 0.4 | 0.6 ± 0.1 | 7.08 ± 0.19 | 13.8 ± 0.5 | 44.4 ± 1.7 | 62.6 ± 1.4 | 19.5 ± 0.4 | 31.1 ± 0.5 | 3.25 ± 0.88 | 950 ± 151 | 17.4 ± 0.5 | 38.5 ± 2.7 |
DW | 6.47 ± 1.21 | 14.6 ± 5.0 | 78.3 ± 5.4 | 2.0 ± 0.3 | 3.1 ± 0.9 ** | 0.8 ± 0.3 | 7.04 ± 0.41 | 13.6 ± 1.0 | 43.8 ± 2.9 | 62.2 ± 1.6 | 19.3 ± 0.5 | 31.0 ± 0.6 | 2.72 ± 0.22 | 902 ± 300 | 17.3 ± 0.9 | 39.0 ± 7.3 |
5% albumin | 6.74 ± 1.22 | 7.9 ± 1.8 | 86.4 ± 1.5 | 2.0 ± 0.2 | 1.8 ± 0.4 | 0.7 ± 0.4 | 7.27 ± 0.34 | 14.0 ± 0.5 | 45.4 ± 1.3 | 62.5 ± 1.3 | 19.2 ± 0.4 | 30.8 ± 0.4 | 2.65 ± 0.55 | 1056 ± 76 | 17.1 ± 0.3 | 46.2 ± 4.8 |
5% glucose | 6.79 ± 1.37 | 9.5 ± 1.2 | 83.7 ± 1.1 | 2.1 ± 0.5 | 2.2 ± 0.4 | 0.8 ± 0.4 | 7.25 ± 0.33 | 13.9 ± 0.6 | 44.5 ± 2.0 | 61.5 ± 1.1 | 19.2 ± 0.5 | 31.2 ± 0.6 | 2.97 ± 0.60 | 1171 ± 121 | 16.7 ± 0.3 | 40.4 ± 13.1 |
Groups | TP | ALB | A/G | T-BIL | ALP | AST | ALT | CREA | BUN | CHOL | TG | GLU | CA | IP | CK | Na | K | Cl |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(g/dL) | (g/dL) | (mg/dL) | (U/L) | (U/L) | (U/L) | (g/dL) | (g/dL) | (g/dL) | (g/dL) | (g/dL) | (g/dL) | (g/dL) | (IU/L) | (mmol/L) | (mmol/L) | (mmol/L) | ||
Control | 6.8 ± 0.2 | 4.4 ± 0.1 | 1.9 ± 0.1 | 0.0 ± 0.0 | 783 ± 131 | 77 ± 6 | 49 ± 5 | 0.54 ± 0.04 | 26.3 ± 4.7 | 88 ± 14 | 82 ± 9 | 299 ± 33 | 12.7 ± 0.3 | 9.4 ± 0.7 | 185 ± 86 | 147.7 ± 0.7 | 5.60 ± 0.30 | 97.4 ± 0.9 |
DW | 6.2 ± 0.1 ** | 4.1 ± 0.1 ** | 2.0 ± 0.1 | 0.0 ± 0.0 | 550 ± 63 * | 72 ± 5 | 48 ± 4 | 0.48 ± 0.02 * | 19.6 ± 2.8 * | 90 ± 8 | 66 ± 15 | 289 ± 18 | 12.1 ± 0.3 * | 10.9 ± 0.8 * | 278 ± 229 | 147.2 ± 1.0 | 6.22 ± 0.22 | 97.9 ± 1.2 |
5% albumin | 6.2 ± 0.2 ** | 4.1 ± 0.2 ** | 1.9 ± 0.1 | 0.0 ± 0.0 | 542 ± 128 * | 74 ± 7 | 56 ± 9 | 0.49 ± 0.03 | 25.4 ± 2.5 | 83 ± 8 | 51 ± 13 * | 247 ± 39 | 12.1 ± 0.3 * | 10.3 ± 0.8 | 191 ± 45 | 148.0 ± 1.6 | 5.84 ± 0.46 | 98.8 ± 1.2 |
5% glucose | 6.1 ± 0.2 ** | 3.9 ± 0.2 ** | 1.8 ± 0.2 | 0.0 ± 0.0 | 592 ± 114 | 71 ± 10 | 48 ± 6 | 0.50 ± 0.02 | 20.0 ± 2.9 | 85 ± 8 | 62 ± 16 | 259 ± 17 | 12.0 ± 0.2 * | 10.4 ± 0.8 | 209 ± 39 | 147.3 ± 1.7 | 5.88 ± 0.40 | 98.7 ± 2.1 |
Organs | Numbers of Animals | Histopathological Findings | Control | DW | 5% Albumin | 5% Glucose |
---|---|---|---|---|---|---|
Liver | 5 | No abnormalities detected | 5 | 5 | 5 | 5 |
Kidney | 5 | No abnormalities detected | 5 | 5 | 4 | 4 |
Tubular degeneration and inflammatory cell infiltration minimal | 0 | 0 | 0 | 1 | ||
Scar, cortical minimal | 0 | 0 | 1 | 0 | ||
Lung | 5 | No abnormalities detected | 5 | 5 | 5 | 5 |
Spleen | 5 | No abnormalities detected | 5 | 5 | 5 | 5 |
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Jung, E.-B.; Yu, J.; Choi, S.-J. Interaction between ZnO Nanoparticles and Albumin and Its Effect on Cytotoxicity, Cellular Uptake, Intestinal Transport, Toxicokinetics, and Acute Oral Toxicity. Nanomaterials 2021, 11, 2922. https://doi.org/10.3390/nano11112922
Jung E-B, Yu J, Choi S-J. Interaction between ZnO Nanoparticles and Albumin and Its Effect on Cytotoxicity, Cellular Uptake, Intestinal Transport, Toxicokinetics, and Acute Oral Toxicity. Nanomaterials. 2021; 11(11):2922. https://doi.org/10.3390/nano11112922
Chicago/Turabian StyleJung, Eun-Been, Jin Yu, and Soo-Jin Choi. 2021. "Interaction between ZnO Nanoparticles and Albumin and Its Effect on Cytotoxicity, Cellular Uptake, Intestinal Transport, Toxicokinetics, and Acute Oral Toxicity" Nanomaterials 11, no. 11: 2922. https://doi.org/10.3390/nano11112922