|
Медико-биологический
информационный портал
|
 |
для специалистов |
|
|
|
Vol. 24, Art. 35 (pp. 461-472) | 2023
Comparative study of the toxic profile of tyrosine kinase inhibitors and traditional anticancer drugs in an experiment
Savateeva-Lubimova T.N., Sivak K.V., Aleksandrov A.G., Stosman K.I., Kazakova S.B.
Federal State Budgetary Institution «Smorodintsev Research institute of influenza» Ministry of Health of the Russian Federation
Brief summary
Liver injury, nephrotoxicity, and hematopoiesis inhibition are the most severe complications of traditional antitumor therapy, which necessitated the development of drugs that selectively affect specific molecular targets in malignant cells. Early identification of various types toxicity biomarkers during innovative antitumor agents usage can contribute to the timely detection and correction of side effects. In the experiment, the toxic profile of imatinib and gefitinib was studied in comparison with cyclophosphamide and methotrexate when administered intragastrically for 14 days at doses equivalent to one therapeutic dose for an adult and exceeding it by 10 times, taking into account the coefficients of dose transfer to rodents. The obtained results demonstrated that imatinib caused a dose-dependent increase in the activity of hepatocyte cytolysis enzymes, lymphopenia and thrombocytopenia, unlike gefitinib, which caused insignificant disorders of the liver and blood system only when used at a dose exceeding the therapeutic dose by 10 times. The widest range of side effects was observed, including indicators of hepatotoxicity, nephrotoxicity and hepatotoxicity, when using cyclophosphamide. The toxicity profile of methotrexate included indicators of hepatotoxicity and hematotoxicity. Key words imatinib; gefitinib; cyclophosphamide; methotrexate; toxicity; rats (The article in PDF format. For preview need Adobe Acrobat Reader)  Open article in new window
Reference list 1.Garin A.M., Bazin I.S. Kratkaya istoriya lekarstvennoi terapii opyholei. Poka eto tretii metod lecheniya raka. Effektivnaya farmakoterapiya. Onkologiya, gematologiya i radiologiya. 2013; 3: 8-13. 2. Davidov M.I. Racionalnaya farmakoterapiya v onkologii / pod red. M.I. Davidova, V.A. Gorbynovoi. M.: Litterra; 2017. URL: https://www.rosmedlib.ru/book/ISBN9785423502447.html (data obrasheniya: 21.02.2023). 3. Falzone L., Salomone S., Libre M. Evolution of cancer pharmacological treatments at the turn of the third millennium. Front. Pharmacol., Sec. Experimental Pharmacology and Drug Discovery. 2018;9:1-26. https://doi.org/10.3389/fphar.2018.01300. 4. Puyo S., Montaudon D., Pourquie P. From old alkylating agents to new minor groove binders. Crit Rev OncolHematol. 2014;89(1):43-61. https://doi.org/10.1016/j.critrevonc.2013.07.006. 5. Peters G.J., van der Wilt C.L., van Moorsel C.J. et al. Basis for effective combination cancer chemotherapy with antimetabolites. PharmacolTher. 2000;87(2-3):227-53. https://doi: 10.1016/s0163-7258(00)00086-3. 6. Sakaeva D.D., Orlova R.V., Shabaeva M.M. Prakticheskie rekomendacii po lecheniu infekcionnih oslojnenii febrilnoi neitropenii i naznacheniu koloniestimyliryushih faktorov y onkologicheskih bolnih. Zlokachestvennie opyholi: Prakticheskie rekomendacii RUSSCO. 2018; 8 (3, specvipysk 2): 521-530. 7. Tkachenko P.E., Ivashkin V.T., Maevskaya M.V. Klinicheskie rekomendacii po korrekcii gepatotoksichnosti, indycirovannoi protivoopyholevoi terapiei. Zlokachestvennie opyholi: Prakticheskie rekomendacii RUSSCO. 2018; 8 (3, specvipysk 2): 531-544. 8. Valiev T.T., Korkina U.S. Ifosfamid/ciklofosfamid-indycirovannaya metgemoglobinemiya pri lechenii gemoblastozov y detei. Sovremennaya onkologiya. 2020; 22 (4): 139-142. https://doi:10.26442/18151434.2020.4.200481 9. Hojjat-Farsangi M. Small-molecule inhibitor the receptor tyrosinekinases: promise therapies. Int. J. Mol Sci. 2014;15(8):13768-801. https://doi: 10.3390/ijms150813768. 10. Tsimberidou A.M. Targeted therapy in cancer. Cancer ChemotherPharmacol. 2015; 76:1113-1132.https://doi.org/10.1007/s00280-015-2861-1. 11. Ayoub N.M. Editorial: novel combination therapies for the treatment of solid cancers. Front Oncol. 2021;18;11:708943. https://doi: 10.3389/fonc.2021.708943. 12. Tan A.C., Bagley S.J., Wen P.Y., et al. Systematic review of combinations of targeted or immunotherapy in advanced solid tumors. Journal for ImmunoTherapy of Cancer. 2021;9:e002459. https://doi:10.1136/ jitc-2021-002459. 13. Zubair T., Bandyopadhyay D. Small molecule EGFR Inhibitors as anti-cancer agents: discovery, mechanisms of action, and opportunities. Int. J. Mol. Sci. 2023, 24(3): 2651. https://doi.org/10.3390/ijms24032651. 14. Wu P., Clausen M.H., Nielsen T.E. Allosteric small-molecule kinase inhibitors. Pharmacol Ther. 2015;156:59-68. https://doi.org/10.1016/j. pharmthera.2015.10.002. 15. Rykovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Chast pervaya. M.: Grif i K.; 2012. 16. Korman D.B. Misheni i mehanizmi deistviya protivoopyholevih preparatov. Moskva: Prakticheskaya medicina; 2014. 17. Emadi A., Jones R.J., Brodsky R.A. Cyclophosphamide and cancer: golden anniversary. Nat Rev ClinOncol. 2009; 6(11):638-47. https://doi:10.1038/nrcclinonc. 2009.146. 18. Chakraborty P., Roy S.S., Basu A., Bhattacharya S. Sensitization of cancer cells to cyclophosphamide therapy by an organoselenium compound through ROS-mediared apoptosis. Biomedicine & Pharmacotherapy. 2016; 84:1992-1999. htpps://doi.org/10.1016/j.biopha.2016.11.006. 19. Shi H., Hou B., Li H., et al. Cyclophosphamide induced thhhheferroptosis of tumor cells through heme oxygenase-1. Front. Pharmacol. 2022; 13. htpps://doi.org/10.3389/ fpharm.2022.839464. 20. Tiwari M. Antimetabolites: established cancer therapy. J. Cancer. Res. Ther. 2012;8(4):510-519. https://doi.org/10.4103/0973-1482.106526. 21. Frolov B.A., Kalinina O.V., Kirillova A.V., Shtil A.A. Preodolenie gepatotoksichnosti metotreksata: rol triterpenoidov. Klinicheskaya onkogematologiya. 2013; 6(1):1-12. 22. Demirci T., Gedicli S., Ozturk N., Celep N.A. The protective effect of N-acetylcysteine against methotrexate-induced hepatotoxicity in rats. EJMI. 2019; 3 (3): 219-226. https://doi: 10.14744/edjmi.2019.42299. 23. Rossari F., Minutolo F., Orciuolo E. Past, present, and future of BcrAbl inhibitors: from chemical development to clinical efficacy. J. Hematol. Oncol. 2018;11(1):84. https://doi.org/10.1186/s13045-018- 0624-2. 24. Loren C.P., Aslan J.E., Rigg R.A. et al. The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear. ThrombRes. 2015;135(1):155-160. https://doi: 10.1016/j.thromres.2014.11.009. 25. Lemmon M.A., Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117-1134. https://doi: 10.1016/j.cell.2010.06.011 26. Sudhesh Dev S., Zainal Abidin S.A., Farghadani R. et al. Receptor tyrosine kinases and their signaling pathways as therapeutic targets of curcumin in cancer. Front. Pharmacol. 2021;12:772510. https://doi: 10.3389/fphar.2021.772510. 27. Baccarani M., Deininger M.W., Rosti G. et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872-884. https://doi: 10.1182/blood-2013-05-501569. 28. Drullion C., Trégoat C., Lagarde V. et al. Apoptosis and autophagy have opposite roles on imatinib-induced K562 leukemia cell senescence. Cell Death Dis. 2012;3(8):e373. https://doi: 10.1038/cddis.2012.111. 29. Zhao Z.Q., Yu Z.Y., Li J., Ouyang X.N. Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway. Oncol Lett. 2016;12(1):63-68. https://doi: 10.3892/ol.2016.4606. 30. Gajski G., Gerić M., Domijan A-M. et al. Evaluation of oxidative stress responses in human circulating blood cells after imatinibmesylate treatment - Implications to its mechanism of action. Saudi Pharm. J. 2019;8:1216-1221. https:// doi: 10.1016/j.jsps.2019.10.005 |
|||||||||
Articles
| Размещение рекламы | |
| |
 |