Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Drug Treatment
2.2. Cell Proliferation and Death
2.3. Enzyme Activity Assays and Albumin Release
2.4. Statistical Analysis
3. Results
3.1. Rifampicin and Cefuroxime Significantly Reduce Vitality and Cell Proliferation in a Dose-Dependent Manner
3.2. Cefuroxime Causes the Highest Dose-Dependent Loss of Cell Integrity (LDH)
3.3. Effects of Antibiotics on the Activity of Mitochondrial Dehydrogenase in Hepatocytes
3.4. Decrease in Cytochrome 1A2 Activity
3.5. Tigecycline Led to a Noticeable Dose-Dependent Impairment of Albumin-Synthesis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Microalbumin [mg/L]. Medium | Microalbumin [mg/L]. Plasma | ||||
---|---|---|---|---|---|---|
Testsubstance | Cmax | 5x Cmax | 10x Cmax | Cmax | 5x Cmax | 10x Cmax |
Ampicillin | 9.37 * 8.64/9.96 | 5.21 * 5.01/5.41 | 4.66 * 4.56/4.84 | 57.65 * 55.83/62.43 | 31.65 18.00/38.43 | 30.15 23.35/48.93 |
Cefepim | 9.23 * 6.93/12.15 | 5.69 4.99/7.83 | 5.44 * 4.78/6.63 | 94.90 * 80.90/106.00 | 85.15 * 72.88/106.80 | 96.90 * 85.40/109.80 |
Cefuroxime | 4.26 * 2.31/5.01 | 1.01 * 0.00/2.77 | 2.16 * 0.00/2.54 | 6.73 * 5.33/7.67 | 5.71 * 5.31/6.63 | 5.88 * 5.23/10.26 |
Levofloxacin | 8.55 6.43/11.93 | 13.45 * 11.98/20.15 | 11.30 * 10.30/14.10 | 134.50 * 99.58/146.80 | 129.00 * 101.00/135.80 | 98.10 * 36.95/147.50 |
Linezolid | 8.87 * 7.85/11.02 | 6.47 5.71/8.91 | 4.35 * 3.03/5.97 | 90.95 * 86.15/108.20 | 94.05 * 79.75/104.70 | 73.80 * 59.98/87.65 |
Meropenem | 9.68 * 8.87/11.60 | 5.43 * 4.83/7.78 | 4.97 * 4.00/6.17 | 21.40 11.58/65.65 | 17.80 10.15/78.20 | 24.90 14.25/66.70 |
Rifampicin | 7.49 5.30/12.43 | 7.49 5.30/12.45 | 6.48 0.00/8.35 | 106.00 * 34.78/136.00 | 32.60 * 19.08/102.50 | 38.65 * 14.95/99.00 |
Tigecyline | 5.57 * 4.48/6.99 | 2.86 * 0.55/3.05 | 0.00 * 0.00/0.00 | 27.95 14.10/60.05 | 35.15 11.43/68.02 | 20.85 6.76/48.50 |
Vancomycin | 7.28 6.35/8.57 | 5.99 * 5.04/6.93 | 6.61 4.99/7.15 | 10.45 8.96/11.55 | 9.97 7.81/13.80 | 12.30 10.28/13.68 |
pos.Ctrl | 0.00 0.00/3.15 | 2.96 3.73/4.95 | ||||
neg. Ctrl | 6.59 5.68/8.78 | 20.40 7.93/50.70 |
neg. Ctrl | Ampicillin | Cefepime | Cefuroxime | Levofloxacin | Linezolid | Meropenem | Rifampicin | Tigecycline | Vancomycin | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Protein binding [%] | 20 | 20 | 50–70 | 30–40 | 30 | 15 | 75–80 | 90 | 50 | |||||||||||
Medium/Plasma | M | P | M | P | M | P | M | P | M | P | M | P | M | P | M | P | M | P | M | P |
Cell Count (×100,000) | 7.8 | 5.6 | ↓ | ↓ | ↓ | ↓ | ↓ | |||||||||||||
Vitality [%] | 94 | 91 | ↓ | ↓ | ↓ | ↓ | ↓ | |||||||||||||
LDH 6d [U/L] | 91 | 168 | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | |||||||||||
XTT (OD) | 1.38 | 1.26 | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ||||||||||
MA [mg/L] | 6.6 | 33.1 | ↓ | ↓ | ↓ | ↓ | ↓ | |||||||||||||
CYP1A2 [pmol/L] | 8.77 | 5.3 | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ | ||||
Hepatotoxic-Potential | ** | * | ** | * | *** | ** | *** | ** | ** | * | ** | ** | **** | * | ***** | **** | **** | *** |
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Doß, S.; Blessing, C.; Haller, K.; Richter, G.; Sauer, M. Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro. Curr. Issues Mol. Biol. 2022, 44, 4639-4657. https://doi.org/10.3390/cimb44100317
Doß S, Blessing C, Haller K, Richter G, Sauer M. Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro. Current Issues in Molecular Biology. 2022; 44(10):4639-4657. https://doi.org/10.3390/cimb44100317
Chicago/Turabian StyleDoß, Sandra, Corinne Blessing, Katharina Haller, Georg Richter, and Martin Sauer. 2022. "Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro" Current Issues in Molecular Biology 44, no. 10: 4639-4657. https://doi.org/10.3390/cimb44100317