Study of hepatotoxins influence in vitro on basic biochemical indicators of liver functional state
DOI:
https://doi.org/10.15587/2519-8025.2021.250223Keywords:
carbon tetrachloride, ciprofloxacin, rat hepatocytes, cytolysis enzymesAbstract
An antimicrobial drug of the fluoroquinolone group, ciprofloxacin, is widely used in Ukraine. However, some researchers have noted the probable hepatotoxicity of this drug with prolonged use or use of high doses of ciprofloxacin. The aim of this study was to compare the effects of carbon tetrachloride, as a classical model of hepatocyte injury, with the effects of ciprofloxacin.
The aim of the study was to investigate the biochemical parameters of the liver when simulating toxic damage to hepatocytes with carbon tetrachloride or ciprofloxacin.
Materials and methods. The study was carried out on isolated rat hepatocytes, in whose culture medium carbon tetrachloride or ciprofloxacin was added. After incubation in the supernatant and cell homogenate, the activities of marker enzymes of cytolysis were determined: ALT, AST, γ-GTP, LF, LDH, DC and MDA.
Results. The introduction of ciprofloxacin into the culture of hepatocytes at a concentration of LC50 caused changes in biochemical parameters similar to those caused by carbon tetrachloride. Thus, an increase in ALT, AST, γ-GTP, LF, LDH, DC and MDA was observed when CCl4 or ciprofloxacin was added to the culture.
Conclusion. Incubation of rat hepatocytes with carbon tetrachloride or ciprofloxacin caused an increase in the level of enzymes and lipid peroxidation products. These parameters are indicators of gross changes in cells, which are the result of impaired keto acid formation, impaired redox reactions, impaired glycogen production
References
- Mohi-ud-din, R., Mir, R. H., Sawhney, G., Dar, M. A., Bhat, Z. A. (2019). Possible Pathways of Hepatotoxicity Caused by Chemical Agents. Current Drug Metabolism, 20 (11), 867–879. doi: http://doi.org/10.2174/1389200220666191105121653
- Unsal, V., Cicek, M., Sabancilar, İ. (2020). Toxicity of carbon tetrachloride, free radicals and role of antioxidants. Reviews on Environmental Health, 36 (2), 279–295. doi: http://doi.org/10.1515/reveh-2020-0048
- Li, X., Chen, Y., Ye, W., Tao, X., Zhu, J., Wu, S., Lou, L. (2015). Experimental research Blockade of CCN4 attenuates CCl 4 -induced liver fibrosis. Archives of Medical Science, 3, 647–653. doi: http://doi.org/10.5114/aoms.2015.52371
- Liu, H. H., Li, A. J. (2020). MiR-340 suppresses CCl4-induced acute liver injury through exerting anti-inflammation targeting Sigirr. European review for medical and pharmacological sciences, 24 (20), 10687–10695. doi: https://doi.org/10.26355/eurrev_202010_23427
- Weber, L. W. D., Boll, M., Stampfl, A. (2003). Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model. Critical Reviews in Toxicology, 33 (2), 105–136. doi: http://doi.org/10.1080/713611034
- Ahmad, W., Waqar, M., Hadi, M. H., Muhammad, A. S., Iqbal, N. (2021). Acute Cholestatic Liver Injury Due to Ciprofloxacin in a Young Healthy Adult. Cureus, 13 (2). doi: http://doi.org/10.7759/cureus.13340
- Koutsandrea, C. N., Miceli, M. V., Peyman, G. A., Farahat, H. G., Niesman, M. R. (1991). Ciprofloxacin and dexamethasone inhibit the proliferation of human retinal pigment epithelial cells in culture. Current Eye Research, 10 (3), 249–258. doi: http://doi.org/10.3109/02713689109003447
- Dong, S., Chen, Q.-L., Song, Y.-N., Sun, Y., Wei, B., Li, X.-Y. et. al. (2016). Mechanisms of CCl4-induced liver fibrosis with combined transcriptomic and proteomic analysis. The Journal of Toxicological Sciences, 41 (4), 561–572. doi: http://doi.org/10.2131/jts.41.561
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (2012). National Institute of Diabetes and Digestive and Kidney Diseases. Ciprofloxacin. Available at: https://www.ncbi.nlm.nih.gov/books/NBK548066/
- Zimpfer, A., Propst, A., Mikuz, G., Vogel, W., Terracciano, L., Stadlmann, S. (2004). Ciprofloxacin-induced acute liver injury: case report and review of literature. Virchows Archiv, 444 (1), 87–89. doi: http://doi.org/10.1007/s00428-003-0917-9
- Goetz, M., Galle, P. R., Schwarting, A. (2003). Non-Fatal Acute Liver Injury Possibly Related to High-Dose Ciprofloxacin. European Journal of Clinical Microbiology and Infectious Diseases, 22 (5), 294–296. doi: http://doi.org/10.1007/s10096-003-0914-6
- Unger, C., Al-Jashaami, L. S. (2016). Ciprofloxacin Exposure Leading to Fatal Hepatotoxicity: An Unusual Correlation. American Journal of Case Reports, 17, 676–681. doi: http://doi.org/10.12659/ajcr.899080
- Petrenko, A. Iu., Sukach, A. N., Rosliakov, A. D. (1991). Vydelenie gepatotsitov krys nefermentativnym metodom: detoksikatsionnaia i dykhatelnaia aktivnosti. Biokhimiia, 56 (9), 1647–1650.
- Freshney, I. (2001). Application of cell cultures to toxicology. Cell biology and toxicology, 17 (4-5), 213–230. doi: https://doi.org/10.1023/a:1012572930721
- Gavrilov, V. B., Mishkorudnaia, M. I. (1989). Spektrofotometricheskoe opredelenie soderzhaniia gidroperekisei lipidov v plazme krovi. Laboratornaia diagnostika ishemicheskoi bolezni serdtsa. Kyiv: Zdorov’ia, 170–171.
- Korobeinikova, E. N. (1989). Modifikatsiia opredeleniia produktov POL v reaktsii s tiobarbiturovoi kislotoi. Laboratornoe delo, 7, 8–10.
- Rahmani, A. H., Almatroudi, A., Babikr, A. Y., Ali Khan, A., Alsahli, M. A. (2019). Thymoquinone, an Active Constituent of Black Seed Attenuates CCl4 Induced Liver Injury in Mice via Modulation of Antioxidant Enzymes, PTEN, P53 and VEGF Protein. Open Access Macedonian Journal of Medical Sciences, 7 (3), 311–317. doi: http://doi.org/10.3889/oamjms.2019.050
- Koyama, T., Hamada, H., Nishida, M., Naess, P. A., Gaarder, C., Sakamoto, T. (2016). Defining the optimal cut-off values for liver enzymes in diagnosing blunt liver injury. BMC Research Notes, 9 (1). doi: http://doi.org/10.1186/s13104-016-1863-3
- Lehmann-Werman, R., Magenheim, J., Moss, J., Neiman, D., Abraham, O., Piyanzin, S. et. al. (2018). Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA. JCI Insight, 3 (12). doi: http://doi.org/10.1172/jci.insight.120687
- Pareek, A., Godavarthi, A., Issarani, R., Nagori, B. P. (2013). Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi) Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line and rats. Journal of Ethnopharmacology, 150 (3), 973–981. doi: http://doi.org/10.1016/j.jep.2013.09.048
- Demiroren, K., Basunlu, M. T., Erten, R., Cokluk, E. (2018). A comparison of the effects of thymoquinone, silymarin and N-acetylcysteine in an experimental hepatotoxicity. Biomedicine & Pharmacotherapy, 106, 1705–1712. doi: http://doi.org/10.1016/j.biopha.2018.07.125
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Liudmyla Maloshtan, Galyna Storozhenko, Liubov Galuzinska, Victoriia Fylymonenko, Omar Rashid Sadiq
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.