Effect of L-Dopa on Carboplatin Induced Hepatotoxicity

Çağatay Oltulu & Nebiye Pelin Türker

doi:https://doi.org/10.29329/ijiasr.2023.524.4

Original article | Open Access
International Journal of Innovative Approaches in Science Research 2023, Vol. 7(1) 37-46

Effect of L-Dopa on Carboplatin Induced Hepatotoxicity

Çağatay Oltulu & Nebiye Pelin Türker

pp. 37 - 46 | DOI: https://doi.org/10.29329/ijiasr.2023.524.4

Published online: March 20, 2023 | Number of Views: 83 | Number of Download: 284

Download PDF

Abstract

Carboplatin is an alkylating antineoplastic drug. Although carboplatin induces apoptosis in rapidly dividing cells like cisplatin, it has fewer side effects. The use of platinum compounds as antineoplastic agents at high doses causes hepatotoxicity, which is important in dose regulation. Levodopa is used as a precursor for dopamine synthesis in the brain in the treatment of Parkinson's disease. Dopamine synthesized in the liver from levodopa cannot cross the blood-brain barrier. There are studies suggesting that dopamine may have a protective effect on hepatocytes. In our study, we aimed to evaluate the cytoprotective effect of levodopa in cell damage induced by carboplatin in the liver cell line. Cell viability was evaluated by MTT test by exposing AML-12 hepatocyte cells to the combination of Carboplatin, L-DOPA and Carboplatin + L-DOPA for 24 hours (0, 3.13, 6.25, 12.5, 25, 50 ,100 µM) has been left. The LD50 value of carboplatin was determined as 62.65 µM. The LD50 values of the combination of L-DOPA and carboplatin + L-DOPA were higher in the tested dose range. The cytotoxic effect of carboplatin on the AML-12 cell line was determined by the increasing LD50 value, which was statistically significantly reduced when combined with levodopa. Further studies are needed to explain the mechanism of action.

Keywords: Liver, L-DOPA, Carboplatin, Cytotoxicity

How to Cite this Article

APA 6th edition
Oltulu, C. & Turker, N.P. (2023). Effect of L-Dopa on Carboplatin Induced Hepatotoxicity . International Journal of Innovative Approaches in Science Research, 7(1), 37-46. doi: 10.29329/ijiasr.2023.524.4

Harvard
Oltulu, C. and Turker, N. (2023). Effect of L-Dopa on Carboplatin Induced Hepatotoxicity . International Journal of Innovative Approaches in Science Research, 7(1), pp. 37-46.

Chicago 16th edition
Oltulu, Cagatay and Nebiye Pelin Turker (2023). "Effect of L-Dopa on Carboplatin Induced Hepatotoxicity ". International Journal of Innovative Approaches in Science Research 7 (1):37-46. doi:10.29329/ijiasr.2023.524.4.

References

1. Livshits Z, Rao RB, Smith SWJEMC. An approach to chemotherapy-associated toxicity. 2014;32(1):167-203.

2. Ali MM, Aziz TAJA-RJoMS. Toxic Effect of Platinum Compounds: Molecular Mechanisms of Toxicity. 2021;1:81-8.

3. Podratz JL, Knight AM, Ta LE, Staff NP, Gass JM, Genelin K, et al. Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons. 2011;41(3):661-8.

4. Desoize B, Madoulet CJCrioh. Particular aspects of platinum compounds used at present in cancer treatment. 2002;42(3):317-25.

5. Doz FJBdc. Carboplatin in pediatrics. 2000;87:25-9.

6. Chatterjee S, Rhee Y-H, Ahn J-C. Sulforaphene–carboplatin combination synergistically enhances apoptosis by disruption of mitochondrial membrane potential and cell cycle arrest in human non-small cell lung carcinoma. Journal of medicinal food. 2016;19(9):860-9.

7. Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition. 2013;29(1):15-21.

8. Erisgin Z, Atasever M, Cetinkaya K, Dizakar SÖA, Omeroglu S, Sahin H. Protective effects of Nigella sativa oil against carboplatin-induced liver damage in rats. Biomedicine & Pharmacotherapy. 2019;110:742-7.

9. Alshorbaji MA, Dabdoub BR. Gum Arabic's Effect on Carboplatin-Induced Hepatotoxicity in Male Rats. NeuroQuantology. 2022;20(8):2547-56.

10. Carboplatin. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD)2012.

11. Özbek H, Uğraş S, Alıcı SJVTD. Rezene uçucu yağının carboplatin’e bağlı hepatotoksisite üzerine koruyucu etkisi. 2003;10(4):91-7.

12. Cao S, Wang C, Ma H, Yin R, Zhu M, Shen W, et al. Genome-wide Association Study on Platinum-induced Hepatotoxicity in Non-Small Cell Lung Cancer Patients. Sci Rep. 2015;5:11556. Epub 2015/06/24. doi: 10.1038/srep11556. PubMed PMID: 26100964; PubMed Central PMCID: PMCPMC4477405.

13. HASSAN ES, MAJEED SA, MOHAMMAD AR, GAEN KKJIJoPR. The protective effect of the N acetylcysteine on acute liver toxicity induced by carboplatin in rat model. International Journal of Pharmaceutical Research. 2019;11(3).

14. Zhou H, Tang L, Yang Y, Lin L, Dai J, Ge P, et al. Dopamine alleviated acute liver injury induced by lipopolysaccharide/d-galactosamine in mice. Int Immunopharmacol. 2018;61:249-55. Epub 2018/06/13. doi: 10.1016/j.intimp.2018.06.004. PubMed PMID: 29894864.

15. Sofian ZM, Shafee SS, Abdullah JM, Osman H, Razak SA. Evaluation of the Cytotoxicity of Levodopa and its Complex with Hydroxypropyl-ß-Cyclodextrin (HP-ß-CD) to an Astrocyte Cell Line. The Malaysian journal of medical sciences: MJMS. 2014;21(Spec Issue):6.

16. Dairman W, Christenson JG, Udenfriend S. Decrease in liver aromatic L-amino-acid decarboxylase produced by chronic administration of L-dopa. Proceedings of the National Academy of Sciences. 1971;68(9):2117-20.

17. Cotzias GC, Papavasiliou PS, Steck A, Duby S. Parkinsonism and levodopa. Clin Pharmacol Ther. 1971;12(2):319-22. Epub 1971/03/01. doi: 10.1002/cpt1971122part2319. PubMed PMID: 5577480.

18. Boukhris W, Kouassi E, Descotes J, Cordier G, Revillard J. Impaired T-dependent immune response in L-dopa treated BALB/c mice. Journal of clinical & laboratory immunology. 1987;23(4):185-9.

19. Sukmanskii OI, Arkhipenko VI, Cherkashina LP. [Role of adrenergic receptors in the mechanism of action of catecholamines and DOPA on proliferative processes]. Biull Eksp Biol Med. 1984;98(7):89-91. Epub 1984/07/01. PubMed PMID: 6147165.

20. Stewart DJ. Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 2007;63(1):12-31. Epub 2007/03/06. doi: 10.1016/j.critrevonc.2007.02.001. PubMed PMID: 17336087.

21. Türker NP, Bağcı U. Effect of Quinoa Plant on Metastasis and Ion Channels of Rat Brain Cancer Glioma Cell Lines. 2019.

22. Türker NP, Bağcı U, Onsekizoğlu-Bağcı P. Investigation of the Anticancer and Proliferative Effect of Broccoli Extract on Du145 Prostate Cancer and MEF Healthy Fibroblast Cell Lines. 2019.

23. Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A. Astroglia in dementia and Alzheimer's disease. Cell Death Differ. 2009;16(3):378-85. Epub 2008/12/06. doi: 10.1038/cdd.2008.172. PubMed PMID: 19057621.

24. Abdel-Salam OM, Sleem AA, Shafee N. The dopamine agonist piribedil exerts hepatoprotective effects on carbon tetrachloride-induced hepatic damage. Comparative Clinical Pathology. 2013;22(3):413-9.

25. Mitchell IM, Pollock JC, Jamieson MP. Effects of dopamine on liver blood flow in children with congenital heart disease. The Annals of thoracic surgery. 1995;60(6):1741-4.

Volume 7 Issue 1

March 2023

All Articles