Sıçanlarda Doksorubisin Kaynaklı Böbrek Hasarı Üzerine Selenyum ve N-(p-Amilsinnamoil) Antranilik Asit’in Etkisi

Yıl 2023, , 1181 - 1191, 17.03.2023

Kenan Yıldızhan , Zübeyir Huyut , Fikret Altındağ , Bünyamin Uçar

https://doi.org/10.33715/inonusaglik.1174849

Cited By: 1

Öz

Doksorubisin (DOXR) en önemli antitümör ilaçlardan biridir. Bununla birlikte, birçok organda ciddi istenmeyen yan etkileri, DOXR'in klinikteki kullanımını sınırlamaktadır. Bu çalışma, DOXR uygulanan sıçanlarda Selenyum (Se) ve N-(p-Amilsinnamoil) antranilik asit'in (ACA) böbrek dokusu üzerindeki etkisini araştırmayı amaçlamıştır. Çalışmada kullanılacak sıçanlar altı gruba ayrıldı (n=10); Kontrol, DMSO, DOXR, DOXR+Se, DOXR+ACA ve DOXR+Se+ACA. Çalışmanın sonunda, sıçanların intrakardiyak kanı ve ayrıca böbrek dokuları alındı. Sıçanların serum örneklerinde üre ve kreatin seviyelerine bakıldı. Ayrıca böbrek dokusunda histopatolojik inceleme H&E boyama ile ve 8-OHdG ekspresyonu immünohistokimyasal analiz ile belirlendi. Se ve ACA tedavilerinden sonra, serum örneklerinde DOXR ile artan üre ve kreatin seviyeleri azaldı (p< 0.05). DOXR uygulanan grupta, glomerüler atrofi, tübüler ve glomerüler dilatasyon, damarlarda tıkanıklık ve tübüler epitel hücrelerinde dejenerasyon gözlenirken, Se ve ACA ile tedavi gruplarda ise önemli derecede düzelme görüldü. Ek olarak Se ve ACA tedavileri, DOXR'in indüklediği 8-OHdG ekspresyonunu azalttı (p< 0.05). Bu bulgular, Se ve ACA'nın, DOXR kaynaklı böbrek hasarından sonra meydana gelebilecek böbrek fonksiyon bozukluğunu ve oksidatif DNA hasarını baskılamak için önemli terapötik ajanlar olarak kullanılabileceğini gösterdi.

Anahtar Kelimeler

8-OHdG, Böbrek, Doksorubisin, N-(p-Amilsinnamoil) antranilik asit, Selenyum.

EFFECT OF SELENIUM AND N-(P-AMYLCINNAMOYL) ANTHRANILIC ACID ON DOXORUBICIN-INDUCED KIDNEY INJURY IN RATS

Öz

Doxorubicin (DOXR) is one of the essential antitumor drugs. However, its serious adverse effects in many organs limit the clinical use of DOXR. This study aimed to investigate the effect of selenium (Se) and N-(p-Amilcinnamoyl) anthranilic acid (ACA) on kidney tissue in DOXR-administered rats. The rats in the study were divided into six groups (n=10); Control, DMSO, DOXR, DOXR+Se, DOXR+ACA and DOXR+Se+ACA. At the end of the study, intracardiac blood was drawn from rats, and kidney tissues were removed. Urea and creatine levels were measured in serum samples of rats. In addition, histopathological examination of kidney tissue was determined by H&E staining, and 8-OHdG expression was determined by immunohistochemical analysis. Urea and creatine levels increased with DOXR decreased in serum samples after Se and ACA treatments (p< 0.05). While glomerular atrophy, tubular and glomerular dilatation, vascular occlusion and degeneration of tubular epithelial cells were observed in the DOXR group, significant improvement was observed in the Se and ACA treatment groups. In addition, Se and ACA treatments reduced DOXR-induced 8-OHdG expression (p< 0.05). These findings indicated that Se and ACA could be used as critical therapeutic agents to suppress renal dysfunction and oxidative DNA damage that can occur after DOXR-induced kidney injury.

Anahtar Kelimeler

8-OHdG, Doxorubicin, Kidney, N-(p-Amylcinnamoyl) anthranilic acid, Selenium.

Kaynakça

• Afsar, T., Razak, S., Almajwal, A. & Al-Disi, D. (2020). Doxorubicin-induced alterations in kidney functioning, oxidative stress, DNA damage, and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction. Saudi Journal of Biological Sciences, 27(9), 2251-2260.
• Ahsan, U., Kamran, Z., Raza, I., Ahmad, S., Babar, W., Riaz, M. & Iqbal, Z. (2014). Role of selenium in male reproduction-A review. Animal Reproduction science, 146(1-2), 55-62.
• AlAsmari, A. F., Ali, N., Alharbi, M., Alqahtani, F., Alasmari, F., Almoqbel, D., …Al-Harbi, N. O. (2022). Geraniol Ameliorates Doxorubicin-Mediated Kidney Injury through Alteration of Antioxidant Status, Inflammation, and Apoptosis: Potential Roles of NF-kappaB and Nrf2/Ho-1. Nutrients, 14(8), 1620.
• Ali, N., AlAsmari, A. F., Imam, F., Ahmed, M. Z., Alqahtani, F., Alharbi, M., AlSwayyed, M., AlAsmari, F., Alasmari, M., Alshammari, A., Fantoukh, O. I. & Alanazi, M. M. (2021). Protective effect of diosmin against doxorubicin-induced nephrotoxicity. Saudi J Biol Sci, 28(8), 4375-4383.
• Altınkaynak, Y., Kural, B., Akcan, B. A., Bodur, A., Özer, S., Yuluğ, E., …Örem, A. (2018). Protective effects of L-theanine against doxorubicin-induced nephrotoxicity in rats. Biomedicine & Pharmacotherapy, 108, 1524-1534.
• Altinoz, E., Oner, Z., Elbe, H., Uremis, N. & Uremis, M. (2021). Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress. Drug Chem Toxicol, 45 (5), 2024-2030.
• Bas, E. & Naziroglu, M. (2019). Selenium attenuates docetaxel-induced apoptosis and mitochondrial oxidative stress in kidney cells. Anti-Cancer Drugs, 30(4), 339-346.
• Cakir, M., Duzova, H., Tekin, S., Taslidere, E., Kaya, G. B., Cigremis, Y., …Yologlu, S. (2017). ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats. Life Sci, 176, 10-20.
• Cardoso, D. F., Coriolano, H.-J. A. & Duarte, J. A. (2018). Regular voluntary running has favorable histological effects on doxorubicin-induced kidney toxicity in Wistar rats. Cell and Tissue Research, 374(1), 177-187.
• Cengiz, O., Baran, M., Balcioglu, E., Suna, P. A., Bilgici, P., Goktepe, O., Onder, G. O., Goc, R. & Yay, A. (2021). Use of selenium to ameliorate doxorubicin induced hepatotoxicity by targeting pro-inflammatory cytokines. Biotech Histochem, 96(1), 67-75.
• Chabner, B. A., Amrein, P. C., Druker, B. J., Michaelson, M. D., Mitsiades, C. S., Goss, P. E., …Supko, J. G. (2006). Antineoplastic agents. The Pharmacological Basis of Therapeutics 9/e, 1315-1465.
• Fouad, G. I. & Ahmed, K. A. (2021). The protective impact of berberine against doxorubicin-induced nephrotoxicity in rats. Tissue and Cell, 73, 101612.
• Fukasawa, H., Furuya, R., Yasuda, H., Yamamoto, T., Hishida, A. & Kitagawa, M. (2014). Anti-cancer agent-induced nephrotoxicity. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 14(7), 921-927.
• Harteneck, C., Frenzel, H. & Kraft, R. (2007). N‐(p‐amylcinnamoyl) anthranilic acid (ACA): a phospholipase A2 inhibitor and TRP channel blocker. Cardiovascular Drug Reviews, 25(1), 61-75.
• Hassan, M. Q., Akhtar, M. S., Afzal, O., Hussain, I., Akhtar, M., Haque, S. E. & Najmi, A. K. (2020). Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity. Clinical and Experimental Hypertension, 42(5), 381-392.
• Hekmat, A. S., Navabi, Z., Alipanah, H. & Javanmardi, K. (2021). Alamandine significantly reduces doxorubicin-induced cardiotoxicity in rats. Hum Exp Toxicol, 40(10), 1781-1795.
• Hosseinzadeh, A., Goudarzi, M., Fatemi, I., Khodayar, M. J., Mehrzadi, S., Khalili, H. R. & Karimi, M. A. (2020). Gemfibrozil attenuates doxorubicin induced toxicity in renal tissues of male rats by reducing the oxidative insult and inflammation. Biotechnic & Histochemistry, 95(7), 532-539.
• Ibrahim Fouad, G. & Ahmed, K. A. (2021). The protective impact of berberine against doxorubicin-induced nephrotoxicity in rats. Tissue Cell, 73, 101612.
• Khames, A., Gad, A. M. & Abd El-Raouf, O. M. (2017). Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats. European Journal of Pharmacology, 805, 118-124.
• Khan, M. A., Singh, D., Arif, A., Sodhi, K. K., Singh, D. K., Islam, S. N., …Siddique, H. R. (2022). Protective effect of green synthesized Selenium Nanoparticles against Doxorubicin induced multiple adverse effects in Swiss albino mice. Life Sciences, 305, 120792.
• Mancilla, T. R., Iskra, B. & Aune, G. J. (2019). Doxorubicin-induced cardiomyopathy in children. Comprehensive Physiology, 9(3), 905.
• Miller, B. A. (2019). TRPM2 in Cancer. Cell Calcium, 80, 8-17.
• Qu, X., Zhai, J., Hu, T., Gao, H., Tao, L., Zhang, Y., Song, Y. & Zhang, S. (2019). Dioscorea bulbifera L. delays the excretion of doxorubicin and aggravates doxorubicin-induced cardiotoxicity and nephrotoxicity by inhibiting the expression of P-glycoprotein in mice liver and kidney. Xenobiotica, 49(9), 1116-1125.
• Rivankar, S. (2014). An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther, 10(4), 853-858.
• Uçar, B., Huyut, Z., Altındağ, F., Keleş, Ö. F. & Yıldızhan, K. (2022). Relationship with nephrotoxicity of Abemaciclib in rats: Protective effect of Curcumin. IJBB, 59(10), 963-976.
• Ugur, S., Ulu, R., Dogukan, A., Gurel, A., Yigit, I. P., Gozel, N., Aygen, B. & Ilhan, N. (2015). The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Renal Failure, 37(2), 332-336.
• Valavanidis, A., Vlachogianni, T. & Fiotakis, C. (2009). 8-hydroxy-2′-deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. Journal of Environmental Science and Health Part C, 27(2), 120-139.
• Wang, Q., Wang, C., Li, S., Xiong, Y., Wang, H., Li, Z., Wan, J., Yang, X. & Li, Z. (2022). Influence of linkers within stimuli-responsive prodrugs on cancer therapy: A case of five doxorubicin dimer-based nanoparticles. Chemistry of Materials, 34(5), 2085-2097.
• Yang, H. B., Lu, Z. Y., Yuan, W., Li, W. D. & Mao, S. (2021). Selenium Attenuates Doxorubicin-Induced Cardiotoxicity Through Nrf2-NLRP3 Pathway. Biol Trace Elem Res. 200, 2848-2856.
• Yildizhan, K., Huyut, Z. & Altindag, F. (2022). Involvement of TRPM2 channel on doxorubicin-induced experimental cardiotoxicity model: Protective role of selenium. Biol Trace Elem Res., in 04 August 2022 retrieved from https://link.springer.com/article/10.1007/s12011-022-03377-2#article-info.
• Zhao, L., Qi, Y., Xu, L., Tao, X., Han, X., Yin, L. & Peng, J. (2018). MicroRNA-140-5p aggravates doxorubicin-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Redox Biol, 15, 284-296.