Cardioprotective effect of all-trans retinoic acid on cisplatin induced cardiotoxicity in rats

Year 2021, , 1230 - 1236, 30.09.2021

Cenk Ekmekci , Sümeyye Ekmekci , Cem Yücel Ebru Çakır

https://doi.org/10.17826/cumj.897675

Abstract

used in the treatment of various tumors. Retinoic acid has potent antioxidant effects. In this study, it is aimed to reveal the effects of all-trans retinoic acid (ATRA) on CP induced cardiotoxicity.
Materials and Methods: In the study, wistar albino rats were used. Control group received single daily doses of 1 ml/kg saline and ATRA group received single daily doses of ATRA(7,5mg/kg/day) intraperitoneally (i.p.) for 10 days. ATRA+CP group received a single dose of CP(7mg/kg) i.p. on the fourth day of the 10 days of ATRA (7,5mg/kg/day) i.p. treatment. The rats in the CP group received only a single dose of cisplatin(7mg/kg) i.p. given on the 4th of 10 days of treatment. After treatment, the groups were compared based on cardiac histopathology findings.
Results: Necrosis, cytoplasmic vacuolization, congestion, hemorrhage and edema were more common in the CP group than the control group). Necrosis and cytoplasmic vacuolization in the all-trans retinoic acid + cisplatin group was observed statistically significantly less frequently than the CP group.
Conclusion: This study confirmed that cisplatin therapy had destructive effects on heart tissue, and showed that all-trans retinoic acid treatment could histopathologically prevent cisplatin-induced cardiotoxicity.

Keywords

Cisplatin, cardiotoxicity, retinoic acid, all-trans retinoic acid

Ratlarda cisplatin kaynaklı kardiyotoksisite üzerine all-trans retinoik asidin kardiyoprotektif etkisi

Abstract

Amaç: Cisplatin, pek çok farklı tümör tedavisinde kullanılan etkili bir antineoplastik ajandır. Retinoik asit güçlü antioksidan etkilere sahiptir. Bu çalışmanın amacı, all-trans retinoik asidin (ATRA) cisplatin kaynaklı kardiyotoksisite üzerine etkilerini araştırmaktır.
Gereç ve Yöntem: Çalışmada wistar albino ratlar kullanıldı. Kontrol grubundaki ratlara 10 gün boyunca günlük 1 ml/kg salin intraperitoneal (i.p.) olarak verildi ve ATRA grubundaki ratlara 10 gün boyunca tek doz (7,5 mg/kg/gün) ATRA i.p. verildi. ATRA + CP grubundaki ratlara 10 gün boyunca tek doz (7,5 mg/kg/gün) ATRA i.p. ve tedavinin dördüncü gününde tek doz CP (7mg/kg) i.p. verildi. CP grubundaki ratlara ise 10 günlük tedavinin dördüncü gününde tek doz CP (7mg/kg) i.p. verildi. Tedaviden sonra gruplar kardiyak histopatoloji bulgularına göre karşılaştırıldı.
Bulgular: Nekroz, sitoplazmik vakuolizasyon, konjesyon, kanama ve ödem cisplatin grubunda kontrol grubuna göre daha yaygındı. All-trans retinoik asid + cisplatin grubunda nekroz ve sitoplazmik vakuolizasyon, CP grubundan istatistiksel olarak anlamlı olarak daha az gözlendi.
Sonuç: Bu çalışma cisplatin tedavisinin kalp dokusu üzerinde yıkıcı etkileri olduğunu doğruladı ve all-trans retinoik asid tedavisinin histopatolojik olarak cisplatine bağlı kardiyotoksisiteyi önleyebildiğini gösterdi.

Keywords

Cisplatin, kardiotoksisite, retinoik asid, all-trans retinoik asid

References

• 1- Smigic J, Sabo T, Vranic A, Zivkovic V, Srejovic I, Turnic TN, et al. Chronic effects of platinum (IV) complex and its diamine ligand on rat heart function: comparison with cisplatin. Mol Cell Biochem. 2019;458(1-2):89-98.
• 2- El-Hawwary AA, Omar NM. The influence of ginger administration on cisplatin-induced cardiotoxicity in rat: Light and electron microscopic study. Acta Histochemica. Acta Histochem. 2019;121(5):553-62.
• 3- Yago-Ibáñez J, García-Pastor C, Lucio-Cazaña FJ, Fernández-Martínez AB. Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death. Biochim Biophys Acta Mol Basis Dis. 2020;1866(7):165795.
• 4- Yucel C, Yucel EE, Arslan FD, Ekmekci S, Kisa E, Ulker V, et al. All-trans retinoic acid prevents cisplatin-induced nephrotoxicity in rats. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(2):159-64.
• 5- Özpolat B. Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments. Turk J Haematol. 2009;26(2):47-61.
• 6- Ewees MG, Abdelghany TM, Abdel-Aziz AA, Abdel-Bakky MS. All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(9):931–938.
• 7- Elsayed AM, Abdelghany TM, Akool el S, Abdel-Aziz AA, Abdel-Bakky MS. All-trans retinoic acid potentiates cisplatininduced kidney injury in rats: impact of retinoic acid signaling pathway. Naunyn Schmiedeberg’s Arch Pharmacol. 2016;389(3):327–337.
• 8- Dugbartey GJ, Peppone LJ, de Graaf IA. An integrative view of cisplatin- induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures. Toxicology 2016; 371: 58-66.
• 9- Aktürk E, Kurtoğlu E, Harputluoğlu H. Cardiovascular Side Effects of Cancer Drugs: How to Identify, Treat, and Follow up These Side Effects İnönü Üniversitesi Tıp Fakültesi Dergisi 2011;18:137-42.
• 10- Demir F, Narin F, Akgün H, Üzüm K, Saraymen R, Baykan A, et al. Effects of melatonin on experimental cardiotoxicity induced by doxorubicin. Çocuk Sağ Hast Derg 2004;47:260-8.
• 11- Demkow U, Biatas-Chromiec B, Stelmaszczyk-Emmel A, Radzikowska E, Wiatr E, Radwan-Rohrenschef P, et al. The Cardiac Markers and Oxidative Stress Parameters in Advanced Non-Small Cell Lung Cancer Patients Receiving Cisplatin-Based Chemotherapy. EJIFCC. 2011;22(1):6-15.
• 12- Hideg K, Kálai T. Novel antioxidants in anthracycline cardiotoxicity. Cardiovasc Toxicol 2007;7:160-4.
• 13- Al-Majed AA, Sayed-Ahmed MM, Al-Yahya AA, Aleisa AM, Al-Rejaie SS, Al-Shabanah OA. Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res. 2006;53(3):278-86.
• 14- Viswanatha Swamy AH, Wangikar U, Koti BC, et al. Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol. 2011;43(5):507-11.
• 15- Topal İ, Bilgin AÖ, Çimen FK, Kurt N, Süleyman Z, Bilgin Y, et al. The effect of rutin on cisplatin-induced oxidative cardiac damage in rats. Anatol J Cardiol. 2018;20(3):136-42.
• 16- Sahna E, Deniz E, Aksulu HE. Myocardial ischemia-reperfusion injury and melatonin. Anadolu Kardiyol Derg 2006; 6: 163-8.
• 17- Tousson E, Hafez E, Zaki S, et al. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environ Sci Pollut Res Int 2016; 23: 20600- 8.
• 18- Dieckmann KP, Struss WJ, Budde U. Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour. Anticancer Res 2011;31(12):4501–5.
• 19- Soliman AF, Anees LM, Ibrahim DM. Cardioprotective effect of zingerone against oxidative stress, inflammation, and apoptosis induced by cisplatin or gamma radiation in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(8):819-32.
• 20- Ibrahim MA, Bakhaat GA, Tammam HG, et al. Cardioprotective effect of green tea extract and vitamin E on Cisplatin-induced cardiotoxicity in mice: Toxicological, histological and immunohistochemical studies. Biomed Pharmacother. 2019;113:108731.
• 21- Lou S, Zhong L, Yang X, Xue T, Gai R, Zhu D, et al. Efficacy of all-trans retinoid acid in preventing nickel induced cardiotoxicity in myocardial cells of rats. Food Chem Toxicol. 2013;51:251-8.
• 22- Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids biochemistry, pharmacology and treatment. Br J Pharmacol 2017; 174: 1290-324.
• 23- Raza S, Ullah K, Ahmed P, Khan B. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia. J Coll Physicians Surg Pak. 2008;18(9):546-50.
• 24- Manolescu DC, Jankowski M, Danalache BA, Wang D, Broderick TL, Chiasson JL, et al. All-trans retinoic acid stimulates gene expression of the cardioprotective natriuretic peptide system and prevents fibrosis and apoptosis in cardiomyocytes of obese ob/ob mice. Appl Physiol Nutr Metab. 2014;39(10):1127-36.
• 25- Gunturk EE, Yucel B, Gunturk I, Yazici C, Yay A, Kose K. The effects of N-acetylcysteine on cisplatin induced cardiotoxicity. Brat Med J. 2019;120 (6): 423-428.