Investigation of the Protective Effects of Caffeic Acid Phenethyl Ester against Cisplatin-induced Liver Damage in Rats

Öz

Cisplatin (CP) is used as an effective chemotherapeutic drug in the treatment of various solid tumors. However, side effects such as hepatotoxicity limit the use of the drug. We investigated the protective effects of caffeic acid phenethyl ester (CAPE), one of the active ingredients of propolis, against hepatotoxicity caused by CP treatment in the liver. 38 Wistar albino rats were divided into 4 groups. Control group was given physiological saline solution for 12 day. CP group was given a single dose of CP (7 mg/kg) on the day 7. CP+CAPE group, was given CAPE (10 μmol/kg/day) for 12 days and a single dose of CP (7 mg/kg) on day 7. CAPE group was given CAPE (10 μmol/kg/day for 12 days. Livers of rats sacrificed on the 14th day were stained with hematoxylin-eosin after histological tissue follow-up. The preparations were evaluated histopathologically and scored. Rat weights were measured and recorded at the beginning and end of the experiment. CP caused significant histopathological changes in the liver. CP also prevented the increase in rat weight. CAPE played an effective role as a protective agent against the histopathological changes caused by CP and showed signs of tissue healing. Our results show that CAPE can be protective against hepatotoxicity associated with CP.

Anahtar Kelimeler

• Caffeic acid phenethyl ester
• cisplatin
• hepatotoxicity
• liver damage
• rat

Kaynakça

1. Pronk L, Schellens J, Planting AT, Van den Bent M, Hilkens P, Van der Burg M, et al. Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. Journal of clinical oncology. 1997;15(3):1071-9.
2. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer. 2007;7(8):573-84.
3. Al‐Majed AA. Carnitine deficiency provokes cisplatin‐induced hepatotoxicity in rats. Basic & clinical pharmacology & toxicology. 2007;100(3):145-50.
4. Amin A, Hamza AA, Kambal A, Daoud S. Herbal extracts counteract cisplatin-mediated cell death in rat testis. Asian journal of andrology. 2008;10(2):291-7.
5. İşeri S, Ercan F, Gedik N, Yüksel M, Alican I. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology. 2007;230(2-3):256-64.
6. Chen X, Wei W, Li Y, Huang J, Ci X. Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis. Chemico-biological interactions. 2019;308:269-78.
7. Quintanilha JCF, Saavedra KF, Visacri MB, Moriel P, Salazar LA. Role of epigenetic mechanisms in cisplatin-induced toxicity. Critical reviews in oncology/hematology. 2019;137:131-42.
8. Bentli R, Parlakpinar H, Polat A, Samdanci E, Sarihan ME, Sagir M. Molsidomine prevents cisplatin-induced hepatotoxicity. Archives of medical research. 2013;44(7):521-8.

9. Ozen S, Akyol O, Iraz M, Söğüt S, Ozuğurlu F, Ozyurt H, et al. Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats. Journal of applied toxicology : JAT. 2004;24(1):27-35.
10. Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia. 2002;73 Suppl 1:S21-9.
11. Omene C, Kalac M, Wu J, Marchi E, Frenkel K, O’Connor OA. Propolis and its active component, caffeic acid phenethyl ester (CAPE), modulate breast cancer therapeutic targets via an epigenetically mediated mechanism of action. Journal of cancer science & therapy. 2013;5(10):334.
12. Ogeturk M, Kus I, Colakoglu N, Zararsiz I, Ilhan N, Sarsilmaz M. Caffeic acid phenethyl ester protects kidneys against carbon tetrachloride toxicity in rats. Journal of ethnopharmacology. 2005;97(2):273-80.
13. Ceylan T, Ünal MA. Patoloji ve Histoloji Laboratuvarı Uygulama Kitabı. Kapadokya Üniversitesi Yayınları; 2020.
14. Akin AT, Kaymak E, Öztürk E, Karabulut D, Kuloğlu N, Ceylan T, et al. Investigation of the Therapeutic Effects of Chloroquine in Adriamycin-Induced Hepatotoxicity. The EuroBiotech Journal. 2021;5(1):8-14.
15. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorganic chemistry. 2019;88:102925.
16. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. European journal of pharmacology. 2014;740:364-78.
17. Bilgic Y, Akbulut S, Aksungur Z, Erdemli ME, Ozhan O, Parlakpinar H, et al. Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity. Experimental and therapeutic medicine. 2018;16(5):4049-57.
18. Boroja T, Katanić J, Rosić G, Selaković D, Joksimović J, Mišić D, et al. Summer savory (Satureja hortensis L.) extract: Phytochemical profile and modulation of cisplatin-induced liver, renal and testicular toxicity. Food and Chemical Toxicology. 2018;118:252-63.
19. Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia. 2002;73:S21-S9.
20. Özen S, Akyol Ö, Iraz M, Söğüt S, Özuğurlu F, Özyurt H, et al. Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin‐induced nephrotoxicity in rats. Journal of Applied Toxicology: An International Journal. 2004;24(1):27-35.
21. Ferreira RS, Dos Santos NAG, Martins NM, Fernandes LS, Dos Santos AC. Caffeic acid phenethyl ester (CAPE) protects PC12 cells from cisplatin-induced neurotoxicity by activating the NGF-signaling pathway. Neurotoxicity Research. 2018;34(1):32-46.
22. Yiğit U, Kırzıoğlu FY, Uğuz AC, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Archives of oral biology. 2017;81:61-8.
23. Salmas RE, Gulhan MF, Durdagi S, Sahna E, Abdullah HI, Selamoglu Z. Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: an experimental and theoretical approach. Cell biochemistry and function. 2017;35(6):304-14.
24. Ceylan T, Kaymak E, Tan FC, Yakan B. Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin. Turkish Journal of Medical Sciences. 2020;50(8):2032-9.