A comparative study of the hepatotrophic properties of non-steroidal anti-inflammatory drugs
Keywords:hepatotoxicity; diclofenac sodium; indomethacin; piroxicam; meloxicam; celecoxib
Topicality. Recently, more and more works on the hepatotoxicity of NSAIDs have appeared in the literature. Presumably, all NSAIDs have hepatotoxicity, but the degree of adverse effects on the liver in different drugs is variable.
Aim. To study the effect of different generations of NSAIDs on the functional state of the liver of the experimental animals.
Materials and methods. Diclofenac sodium, piroxicam, indomethacin, meloxicam and celecocosib were selected for the comparative study. Changes in the functional state of the liver of intact rats during subchronic administration of the drugs selected, as well as their impact on the course of the model hepatitis were determined. The state of the liver was determined by the following indicators: the mass coefficient of the liver, the activity of alanine aminotransferase, alkaline phosphatase, the content of total protein, urea, cholesterol in the blood serum, the level of TBA-active products, diene conjugates, reduced glutathione, catalase and glycogen in the liver homogenate.
Results and discussion. It was found that diclofenac, piroxicam, indomethacin in the doses of ED50 by the antiexudative activity when used for 14 days adversely affected the liver of intact animals, as well as worsened the course of the model hepatitis, i.e. had a pronounced hepatotoxic effect. Meloxicam and celecoxib did not show a pronounced adverse effect in the carbon tetrachloride hepatitis, but contributed to the deterioration of the functional state of the liver of intact rats, i.e. had a moderate hepatotoxic effect.
Conclusions. By the level of hepatotoxicity the drugs studied can be arranged as follows: diclofenac > indomethacin > piroxicam > meloxicam > celecoxib.
Shchokina, K. H. (2006). Eksperymentalne obgruntuvannia ratsionalnoho vyboru suchasnykh i perspektyvnykh preparativ z protyzapalnoiu diieiu. Candidates thesis. Kharkiv, 202.
Bikkinina, G. M., Safuanov, А. P. (2015). Undesirable drug reactions of non-steroidal anti-inflammatory drugs. Young scientist, 7 (87), 269–272. Available at: https://moluch.ru/archive/87/16884/.
Karateev, A. E., Nasonov, E. L., Yakhno, N. N., Ivashkin, V. T. (2015). Sovremennaia revmatolohyia, 9 (1), 23. doi: https://doi.org/10.14412/1996-7012-2015-1-4-23.
Shtrygol, S. Yu. (2005). Provizor, 2, 37–42.
Rostom, A., Goldkind, L., Laine, L. (2005). Nonsteroidal Anti-Inflammatory Drugs and Hepatic Toxicity: A Systematic Review of Randomized Controlled Trials in Arthritis Patients. Clinical gastroenterology and hepatology, 3 (5), 489–498. doi: https://doi.org/10.1016/S1542-3565(04)00777-3.
Sriuttha, P., Sirichanchuen, B., Permsuwan, U. (2018). Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials. International Journal of Hepatology, 1, 1–13. doi: https://doi.org/10.1155/2018/5253623.
Meunier, L., Larrey, D. (2018). Recent Advances in Hepatotoxicity of Non Steroidal Anti-inflammatory Drugs. Annals of Hepatology, 17 (2), 187–191. doi: https://doi.org/10.5604/01.3001.0010.8633.
Schmeltzer, P. A., Kosinski, A. S., Kleiner, D. E., Hoofnagle, J. H., Stolz, A., Fontana, R. J., Russo, M. W. et al. (2016). Liver injury from nonsteroidal anti-inflammatory drugs in the United States Liver Int OffJ Int Assoc Study Liver, 36, 603–609. doi: https://doi.org/10.1111/liv.13032.
Mamchur, V., Podpletnia, Е., Makarenko, О. et al. (2005). Visnyk farmakolohii ta farmatsii, 4, 3–17.
Zhuravleva, M. V., Kukes, V. G., Prokofiev, A. B., Serebrova, S. Yu., Horodetskaia. G. I., Berdnikova. N. H. (2016). Mezhdunarodnyi zhurnal prikladnykh i fundamentalnykh issledovanii, 6 (4), 687–696.
Nicose, S., Arora, M., Singh, P. K. (2015). Hepatotoxicity and Changes in Liver Enzymes Due to Use of Non-Steroidal Anti Inflammatory Drugs (NSAIDs) in Non-Traumatic Musculoskeletal Painful Disorders. Molecular Enzymolody and drug targets, 1 (2-3), 1–6. doi: https://doi.org/10.21767/2572-5475.10007.
Wiley, F. (2020). NSAID-Induced Hepatotoxicity Rare, but Still Important to Note. Drug Topics Journal, 164 (4), 20.
Wondrakpanich, S., Wongrakpanich, A., Melhado, K., Rangaswami, J. (2018). A comprehensive review of nonsteroidal anti-inflammatory drug use in the elderly. Aging Dis., 9 (1), 143–150. doi: 10.14336/AD.20170306.
Khabriev, R. U. (Ed.). (2005). Rukovodstvo po eksperimentalnomu (doklinicheskomu) izucheniiu novykh farmakologicheskikh veshchestv. 2nd ed. Moscow: Meditcina, 832.
Kamyshnikov, V. S. (2002). Spravochnik po klinichesko-biokhimicheskoi laboratornoi diagnostike. (Vols. 1-2). Minsk: Belarus.
Arutiunian, A. V., Dubina, E. E. (2000). Metody otcenki svobodno-radikalnogo okisleniia i antioksidantnoi sistemy organizma. Saint Petersburg: Foliant, 104.
Larrey, D., Ursic-Bedoya, J., Meunier, L. (2018). Drug-Induced hepatotoxicity. Schiff ‘s diseases of the liver. E. R. Schiff (Ed.). 12th ed. New York: Wiley- Blackwell, 740–773.
Chen, M., Suzuki, A., Borlak, J., Andrade, R. J., Lucena, M. I. (2015). Drug-induced liver injury: Interactions between drug properties and host factors. Journal of Hepatology, 63 (2), 503–514. doi: https://doi.org/10.1016/j.jhep.2015.04.016.
Copyright (c) 2021 National University of Pharmacy
This work is licensed under a Creative Commons Attribution 4.0 International License.Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).