Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation and Characterization of Pristine C60 Fullerene Aqueous Colloid Solution (C60FAS)
2.2. In Vitro Assays
2.2.1. Cell Viability and Apoptosis Assays
2.2.2. Immunohistochemical Assay
2.2.3. Biochemical Assays
2.3. Animal Assay
2.3.1. Design of the Study
2.3.2. Survival Assay
2.3.3. Blood Assays
2.3.4. Histological Assays
2.3.5. Liver Assays
2.4. Enzyme Assays
2.5. Statistical Analysis
3. Results
3.1. C60FAS Characterization
3.2. HepG2 Assays
3.3. Survival Assay
3.4. Liver Assays
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Parameters | C60FAS 0 µg/mL (Control) | C60FAS 10 µg/mL | C60FAS 100 µg/mL |
---|---|---|---|
Vim H-score | 13.0 ± 1.3 | 25.1 ± 3.4 * p = 0.012 | 36.8 ± 5.1 * p = 0.003 |
p53 H-score | 18.2 ± 2.2 | 31.5 ± 4.1 * p = 0.02 | 33.9 ± 4.8 * p = 0.006 |
CAT, µmol/mg prot per min | 1551.8 ± 27.1 | 1458.9 ± 55.3 | 1151.3 ± 22.7 * p < 0.001 |
SOD, U/mg prot | 14.68 ± 1.14 | 28.4 ± 0.41 * p < 0.001 | 19.17 ± 0.62 * p = 0.016 |
GSH, nmol/mg prot | 1.43 ± 0.17 | 1.31 ± 0.09 | 0.89 ± 0.002 * p = 0.007 |
GP, nmol/mg prot per min | 0.29 ± 0.01 | 0.31 ± 0.02 | 0.23 ± 0.01 * p = 0.063 |
GST, nmol/mg prot per min | 0.49 ± 0.08 | 0.54 ± 0.02 | 0.26 ± 0.01 * p = 0.013 |
PCG, nmol/mg prot | 29.27 ± 7.14 | 23.81 ± 10.94 | 1.56 ± 0.62 * p = 0.01 |
MDA, nmol/mg prot | 23.32 ± 6.47 | 151.91 ± 39.98 * p = 0.008 | 58.53 ± 6.59 |
LDH, µmol/mg prot per min | 1.48 ± 0.14 | 2.42 ± 0.3 * p = 0.001 | 1.79 ± 0.08 |
G6PD, µmol/mg prot per min | 6.99 ± 0.24 | 3.75 ± 0.45 * p < 0.001 | 0.06 ± 0.04 * p < 0.001 |
Markers | Control | C60FAS | HCC | HCC + 5FU | HCC + C60FAS |
---|---|---|---|---|---|
Direct (conjugated) bilirubin, µmol/L | 4.3 ± 0.35 | 3.95 ± 0.28 | 11.65 ± 0.33 * p < 0.001 | 6.70 ± 0.85 * p = 0.052 # p = 0.001 | 4.55 ± 0.82 # p < 0.001 |
Total bilirubin, µmol/L | 13.04 ± 1.54 | 16.43 ± 1.8 | 30.47 ± 0.87 * p < 0.001 | 19.56 ± 2.22 * p = 0.07 # p = 0.007 | 13.31 ± 1.74 # p < 0.001 |
Non-conjugated bilirubin, µmol/L | 8.64 ± 1.59 | 12.49 ± 1.65 | 18.82 ± 0.6 * p = 0.003 | 12.86 ± 1.84 # p = 0.097 | 8.76 ± 1.18 # p = 0.005 |
Urea, mmol/L | 2.13 ± 0.59 | 3.46 ± 0.31 | 2.51 ± 0.39 | 3.38 ± 0.29 | 3.63 ± 0.53 |
Total protein, g/L | 45.51 ± 1.87 | 47.0 ± 1.34 | 60.63 ± 1.36 * p = 0.015 | 41.24 ± 4.98 # p = 0.005 | 50.4 ± 2.03 |
ALP, µmol/L per min | 333.31 ± 46.05 | 335.05 ± 32.7 | 405.05 ± 2.89 | 280.42 ± 24.06 | 303.16 ± 41.86 |
Triglycerides, mmol/L | 2.55 ± 0.32 | 5.67 ± 1.96 * p = 0.067 | 2.25 ± 0.03 | 1.87 ± 0.19 | 7.13 ± 1.07 * p = 0.003 # p = 0.002 |
LDH, IU/L | 165.65 ± 24.39 | 151.39 ± 35.12 | 180.89 ± 5.5 | 188.36 ± 34.45 | 228.43 ± 34.72 |
α-amylase, g/L per h | 106.34 ± 7.22 | 28.42 ± 16.94 * p = 0.001 | 98.2 ± 10.09 | 47.14 ± 15.34 * p = 0.004 # p = 0.031 | 9.48 ± 4.09 * p < 0.001 # p = 0.001 |
ALT, µmol/mL per h | 1.59 ± 0.1 | 1.25 ± 0.21 | 2.06 ± 0.36 | 1.83 ± 0.33 | 1.74 ± 0.15 |
AST, µmol/mL per h | 1.71 ± 0.05 | 1.6 ± 0.11 | 2.97 ± 0.19 * p < 0.001 | 2.54 ± 0.14 * p = 0.001 | 2.63 ± 0.11 * p < 0.001 |
GGT, IU/L | 1.52 ± 0.11 | 1.79 ± 1.19 | 7.28 ± 0.38 * p = 0.03 | 7.35 ± 2.12 * p = 0.018 | 6.18 ± 0.4 * p = 0.06 |
Markers | Control | C60FAS | HCC | HCC + 5FU | HCC + C60FAS |
---|---|---|---|---|---|
Median survival | N/A | N/A | 17 [23;3] | 30 [32;7] | 31 [35;30] # p = 0.047 |
Macro-scoring | 0 | 0 | 10 [10;11] * p < 0.001 | 10 [5;12] * p < 0.001 | 7 [4.75;10] * p < 0.001 |
Ischak scoring | 0 | 0 | 5 [5;5] * p < 0.001 | 3 [2.25;3.38] *p < 0.001 # p = 0.031 | 3.25 [2.25;3.88] * p < 0.001 # p = 0.032 |
CAT, mmol/mg prot per min | 1.02 [0.76;1.28] | 1.35 [0.83;2.12] | 1.93 [1.02;2.01] | 0.84 [0.72;1.06] # p = 0.077 | 0.81 [0.72;0.95] # p = 0.034 |
SOD, U/mg prot | 34.26 [27.87;40.75] | 71.34 [35.87;88.01] * p = 0.095 | 266.0 [186.48;270.0] * p = 0.025 | 29.59 [22.79;34.09] # p = 0.034 | 48.71 [35.74;52.31] # p = 0.034 |
GSH, nmol/mg prot | 0.16 [0.12;0.23] | 0.2 [0.11;0.27] | 0.24 [0.21;0.3] * p = 0.099 | 0.16 [0.11;0.31] | 0.23 [0.13;0.28] |
GP, nmol/mg prot per min | 0.26 [0.15;0.73] | 0.27 [0.2;0.35] | 0.35 [0.34;0.36] | 0.16 [0.1;0.28] # p = 0.032 | 0.29 [0.17;0.35] # p = 0.067 |
GST, nmol/mg prot per min | 53.66 [49.19;97.8] | 88.78 [33.04;185.82] | 125.12 [84.03;130.34] | 80.69 [53.29;110.82] | 50.08 [33.53;71.6] # p = 0.034 |
PCG, nmol/mg prot | 49.5 [27.29;71.72] | 68.76 [41.68;150.13] | 192.83 [51.87;215.03] | 113.7 [54.92;150.46] | 141.11 [112.06;150.92] * p = 0.014 |
MDA, nmol/mg prot | 76.67 [44.98;100.0] | 160.02 [60.11; 176.67] * p = 0.074 | 281.0 [96.64;310.11] * p = 0.072 | 130.86 [85.05;193.34] * p = 0.086 | 71.71 [65.0;115.83] # p = 0.077 |
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Kuznietsova, H.; Dziubenko, N.; Herheliuk, T.; Prylutskyy, Y.; Tauscher, E.; Ritter, U.; Scharff, P. Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat. Pharmaceutics 2020, 12, 794. https://doi.org/10.3390/pharmaceutics12090794
Kuznietsova H, Dziubenko N, Herheliuk T, Prylutskyy Y, Tauscher E, Ritter U, Scharff P. Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat. Pharmaceutics. 2020; 12(9):794. https://doi.org/10.3390/pharmaceutics12090794
Chicago/Turabian StyleKuznietsova, Halyna, Natalia Dziubenko, Tetiana Herheliuk, Yuriy Prylutskyy, Eric Tauscher, Uwe Ritter, and Peter Scharff. 2020. "Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat" Pharmaceutics 12, no. 9: 794. https://doi.org/10.3390/pharmaceutics12090794