Protective Effects of Montelucast and N-Acetlycystein Activity on Doxorubicin-Induced Liver Damage in Animal Model: Paraoxonase and Arylesterase


Abstract views: 30 / PDF downloads: 15

Authors

  • Suat ÇAKINA Çanakkale Onsekiz Mart University
  • ÖZTÜRK Şamil
  • Latife Ceyda İRKİN

DOI:

https://doi.org/10.5281/zenodo.11373515

Keywords:

oxidative stress, Doxorubicin, N-Acetylcysteine, Montelukast, Liver

Abstract

Objective:  Doxorubicin (DOX) is a chemotherapeutic agent and is widely used in cancer treatment.  There are some studies suggesting oxidative stress-induced toxic changes in the liver due to DOX administration.  The aim of this study was to reveal the oxidative damage of DOX in liver tissue at molecular level and to evaluate the protective effect of N-acetyl cysteine and Montelukast against DOX oxidative damage.

Methods:  Thirty-six male rats were equally divided into 6 groups. The first group was used as control. The second group received a single dose of DOX. The third and fourth groups received N-Acetylcysteine and Montelukast respectively for 28 days.  The fifth and sixth groups received a single dose of DOX, followed by N-Acetylcysteine and Montelukast for 28 days. NAC was given for 10 days. At the end of the experiment, liver tissues were taken from all animals under anesthesia.  Malondialdehyde (MDA), Paraoxanase and Arylesterase levels were determined in these samples by spectrophotometric methods.

Results: It was determined that MDA level increased, paraoxanase and arylesterase levels decreased in the group given Doxo compared to the control group. In addition, MDA and Paraoxanase levels increased in the Doxorubicin+N-Acetylsitein group, but did not approach the control group levels.

Conclusion: It was concluded that Doxorubicin administration increased oxidative stress and NAC administration could prevent the increased oxidative stress. NAC caused modulatory effects on oxidative stress and antioxidant redox system in Doxorubicin-induced liver toxicity in the rat.

Author Biographies

Suat ÇAKINA , Çanakkale Onsekiz Mart University

 

 

ÖZTÜRK Şamil

 

 

Latife Ceyda İRKİN

 

 

References

AlAsmari, A. F., Alharbi, M., Alqahtani, F., Alasmari, F., AlSwayyed, M., Alzarea, S. I., Ali, N. (2021). Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study. Antioxidants (Basel), 10(12). doi:10.3390/antiox10121998.

BahÇEcİOĞLu, İ. H., & Yilmaz, S. (2000). Karbontetraklorür ile siroz oluşturulmuş ratlarda lipid peroksidasyonu, antioksidant enzim ve privat kinaz aktiviteleri. Turkish Journal of Veterinary and Animal Sciences, 24(1), 25-28.

Bilgic, S., & Ozgocmen, M. (2019). The protective effect of misoprostol against doxorubicin induced liver injury. Biotech Histochem, 94(8), 583-591. doi:10.1080/10520295.2019.1605457.

Bulucu, F., Ocal, R., Karadurmus, N., Sahin, M., Kenar, L., Aydin, A., Yaman, H. (2009). Effects of N-acetylcysteine, deferoxamine and selenium on doxorubicin-induced hepatotoxicity. Biol Trace Elem Res, 132(1-3), 184-196. doi:10.1007/s12011-009-8377-y.

Chen, C. F., Hsueh, C. W., Tang, T. S., Wang, D., Shen, C. Y., & Pei, J. S. (2007). Reperfusion liver injury-induced superoxide dismutase and catalase expressions and the protective effects of N-acetyl cysteine. Transplant Proc, 39(4), 858-860. doi:10.1016/j.transproceed.2007.02.018.

Coskun, A. K., Yigiter, M., Oral, A., Odabasoglu, F., Halici, Z., Mentes, O., Suleyman, H. (2011). The effects of montelukast on antioxidant enzymes and proinflammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture-induced sepsis. ScientificWorldJournal, 11, 1341-1356. doi:10.1100/tsw.2011.122.

Gil, F., Pla, A., Gonzalvo, M. C., Hernández, A. F., & Villanueva, E. (1993). Rat liver paraoxonase: subcellular distribution and characterization. Chem Biol Interact, 87(1-3), 149-154. doi:10.1016/0009-2797(93)90036-x.

Im, D. Y., & Lee, K. I. J. T. K. J. o. M. C. S. (2011). Antioxidative and Antibacterial Activity and Tyrosinase Inhibitory Activity of the Extract and Fractions from Taraxacum coreanum Nakai. 19, 238-245.

Injac, R., Boskovic, M., Perse, M., Koprivec-Furlan, E., Cerar, A., Djordjevic, A., & Strukelj, B. (2008). Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress. Pharmacol Rep, 60(5), 742-749.

Kara, Ö., & Kilitçi, A. (2023). Efficacy of Taraxacum officinale in liver damage caused by doxorubicin in rats: Taraxacum and doxorubicin-induced liver toxicity. Journal of Surgery and Medicine, 7(6), 379-382. doi:10.28982/josam.7464.

Kilciksiz, S., Demirel, C., Erdal, N., Gürgül, S., Tamer, L., Ayaz, L., & Ors, Y. (2008). The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model. Acta Med Okayama, 62(6), 403-409. doi:10.18926/amo/30946.

Koçkar, M. C., Nazıroğlu, M., Celik, O., Tola, H. T., Bayram, D., & Koyu, A. (2010). N-acetylcysteine modulates doxorubicin-induced oxidative stress and antioxidant vitamin concentrations in liver of rats. Cell Biochem Funct, 28(8), 673-677. doi:10.1002/cbf.1707.

Koleini, N., Nickel, B. E., Edel, A. L., Fandrich, R. R., Ravandi, A., & Kardami, E. (2019). Oxidized phospholipids in Doxorubicin-induced cardiotoxicity. Chem Biol Interact, 303, 35-39. doi:10.1016 /j. cbi.2019.01.032.

Liu, Y., Zhang, H., Zhang, L., Zhou, Q., Wang, X., Long, J., Zhao, W. (2007). Antioxidant N-acetylcysteine attenuates the acute liver injury caused by X-ray in mice. Eur J Pharmacol, 575(1-3), 142-148. doi:10.1016/j.ejphar.2007.07.026.

Maheswari, E., Saraswathy, G. R., & Santhranii, T. (2014). Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats. Indian J Pharmacol, 46(2), 211-215. doi:10.4103/0253-7613.129321.

Mansour, H. H., Hafez, H. F., Fahmy, N. M., & Hanafi, N. (2008). Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol, 75(3), 773-780. doi:10.1016/j.bcp.2007.09.018.

Mohamadin, A. M., Elberry, A. A., Elkablawy, M. A., Gawad, H. S., & Al-Abbasi, F. A. (2011). Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology, 18(3), 235-242. doi:10.1016/j. pathophys. 2011.02.003.

Nurlu Ayan, N., Karasu, C., & Kavutçu, M. (2019). The Protective Effect of Stobadine on Lipid Peroxidation and Paraoxonase-1 Enzyme Activity in the Liver Tissues of Streptozotocin- Induced Diabetic Rats. Medeniyet Medical Journal, 34(1), 76-82. doi:10.5222/MMJ.2019. 73383.

Osataphan, N., Phrommintikul, A., Chattipakorn, S. C., & Chattipakorn, N. (2020). Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: Insights for future interventions. J Cell Mol Med, 24(12), 6534-6557. doi:10.1111/jcmm.15305.

Ozcelik, M., Erisir, M., Güler, O., & Baykara, M. (2020). The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 17, 195-200. doi:10.32707/ercivet.828349.

Park, E. S., Kim, S. D., Lee, M. H., Lee, H. S., Lee, I. S., Sung, J. K., & Yoon, Y. S. (2003). Protective effects of N-acetylcysteine and selenium against doxorubicin toxicity in rats. J Vet Sci, 4(2), 129-136.

Park, M.-S., So, J.-S., & Bahk, G.-J. (2015). Antioxidative and Anticancer Activities of Water Extracts from Different Parts of Taraxacum coreanum Nakai Cultivated in Korea. Journal of the Korean Society of Food Science and Nutrition, 44, 1234-1240. doi:10.3746/ jkfn.2015. 44.8. 1234.

Powell, S. R., & McCay, P. B. (1995). Inhibition of doxorubicin-induced membrane damage by thiol compounds: toxicologic implications of a glutathione-dependent microsomal factor. Free Radic Biol Med, 18(2), 159-168. doi:10.1016/0891-5849(94)00109-w.

Prasanna, P. L., Renu, K., & Valsala Gopalakrishnan, A. (2020). New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sciences, 250, 117599. doi:https:// doi. Org/10.1016/j.lfs.2020.117599.

Sener, G., Kabasakal, L., Cetinel, S., Contuk, G., Gedik, N., & Yeğen, B. C. (2005). Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs. Burns, 31(5), 587-596. doi:10.1016/j.burns.2005.01.012.

Tuğtepe, H., Sener, G., Cetinel, S., Velioğlu-Oğünç, A., & Yeğen, B. C. (2007). Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a selective leukotriene CysLT1 receptor antagonist. Eur J Pharmacol, 557(1), 69-75. doi:10.1016/j.ejphar.2006.11.009.

Yavaş, M. C., & Kilitci, A. (2023). The effect of radiofrequency electromagnetic radiation on rat liver tissue and serum paraoxonase (PON1). Annals of Medical Research, 30(10), 1245-1249. doi:10.5455/annalsmedres.2023.08.210.

Published

2024-05-29

How to Cite

ÇAKINA , S., Şamil , ÖZTÜRK, & İRKİN , L. C. (2024). Protective Effects of Montelucast and N-Acetlycystein Activity on Doxorubicin-Induced Liver Damage in Animal Model: Paraoxonase and Arylesterase . GEVHER NESIBE JOURNAL OF MEDICAL AND HEALTH SCIENCES, 9(2), 199–206. https://doi.org/10.5281/zenodo.11373515

Issue

Section

Articles