Effects of Oleuropein on Epirubicin and Cyclophosphamide Combination Treatment in Rats

Overview

Journal Turk J Pharm Sci

Specialty Pharmacology

Date 2021 Sep 9

PMID 34496482

Citations 5

Authors

Metin Deniz Karakoc

Selim Sekkin

Affiliations

Soon will be listed here.

Abstract

Objectives: Oleuropein is the main bioactive polyphenolic compound in olive leaves, olive, and olive oil. Its anticancer, antioxidant, and antiinflammatory effects have been proven through several and studies. This study aimed to explore the effects of oleuropein on cyclophosphamideand epirubicin-induced toxicity in female rats.

Materials And Methods: Seven groups containing eight rats in each group were formed. Four cycles of 16 mg/kg/week of cyclophosphamide and 2.5 mg/kg/week of epirubicin were administered to the rats through intraperitoneal injection. Oleuropein (150 mg/kg/week) was simultaneously applied via oral gavage. The effects of oleuropein were examined with hemogram tests in whole blood samples and biochemical analysis in serum samples. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum samples were analyzed through enzyme-linked immunosorbent assay. Subsequently, a comet assay was performed using lymphocyte DNA. The levels of oxidant [i.e., malondialdehyde (MDA)] and antioxidants [i.e., catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD)] were measured in the heart, kidney, and liver tissues.

Results: Oleuropein could reduce DNA damage and serum TNF-α and IL-6 levels. It also ameliorated some hemogram and biochemical parameters that deteriorated due to antineoplastic drugs. It increased the amounts of antioxidants (GSH, SOD, and CAT) and reduced the level of MDA in the heart, kidney, and liver tissues.

Conclusion: Oleuropein might be a beneficial agent against toxicity caused by the combination treatment of cyclophosphamide and epirubicin. Further studies should be performed to demonstrate the protective effects of oleuropein against antineoplastic induced-toxicity precisely.

Citing Articles

Magnolin alleviates cyclophosphamide-induced oxidative stress, inflammation, and apoptosis via signaling pathway.

Ince S, Demirel H, Demirkapi E, Kucukkurt I, Eryavuz A, Arslan-Acaroz D Toxicol Res (Camb). 2024; 13(4):tfae129.

PMID: 39148957 PMC: 11323662. DOI: 10.1093/toxres/tfae129.

Boswellic Acid and Betulinic Acid Pre-treatments Can Prevent the Nephrotoxicity Caused by Cyclophosphamide Induction.

Berkoz M, Ciftci O Dokl Biochem Biophys. 2024; 517(1):115-126.

PMID: 38744737 DOI: 10.1134/S1607672924600234.

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine.

Gervasi F, Pojero F Biomedicines. 2024; 12(3).

PMID: 38540115 PMC: 10968586. DOI: 10.3390/biomedicines12030502.

Cardioprotective effect of oleuropein in a cisplatin-induced cardiotoxicity model in rats.

Gokcek I Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(5):3403-3410.

PMID: 37955692 DOI: 10.1007/s00210-023-02828-4.

Effects of Oleuropein and Hydroxytyrosol on Inflammatory Mediators: Consequences on Inflammaging.

Pojero F, Aiello A, Gervasi F, Caruso C, Ligotti M, Calabro A Int J Mol Sci. 2023; 24(1).

PMID: 36613822 PMC: 9820525. DOI: 10.3390/ijms24010380.

References

Kalaiselvan I, Dicson S, Kasi P . Olive oil and its phenolic constituent tyrosol attenuates dioxin-induced toxicity in peripheral blood mononuclear cells via an antioxidant-dependent mechanism. Nat Prod Res. 2014; 29(22):2129-32. DOI: 10.1080/14786419.2014.989393. View

Alirezaei M, Rezaei M, Hajighahramani S, Sookhtehzari A, Kiani K . Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats. J Physiol Sci. 2016; 67(1):131-139. PMC: 10717304. DOI: 10.1007/s12576-016-0446-3. View

Ryu S, Choi H, Yoon K, Lee O, Kim K, Lee B . Oleuropein suppresses LPS-induced inflammatory responses in RAW 264.7 cell and zebrafish. J Agric Food Chem. 2015; 63(7):2098-105. DOI: 10.1021/jf505894b. View

Andreadou I, Mikros E, Ioannidis K, Sigala F, Naka K, Kostidis S . Oleuropein prevents doxorubicin-induced cardiomyopathy interfering with signaling molecules and cardiomyocyte metabolism. J Mol Cell Cardiol. 2014; 69:4-16. DOI: 10.1016/j.yjmcc.2014.01.007. View

Kurauchi K, Nishikawa T, Miyahara E, Okamoto Y, Kawano Y . Role of metabolites of cyclophosphamide in cardiotoxicity. BMC Res Notes. 2017; 10(1):406. PMC: 5557551. DOI: 10.1186/s13104-017-2726-2. View

Dunning S, Rehman A, Tiebosch M, Hannivoort R, Haijer F, Woudenberg J . Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim Biophys Acta. 2013; 1832(12):2027-34. DOI: 10.1016/j.bbadis.2013.07.008. View

Mahmoudi A, Hadrich F, Feki I, Ghorbel H, Bouallagui Z, Marrekchi R . Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats. Food Funct. 2018; 9(6):3220-3234. DOI: 10.1039/c8fo00248g. View

Katanov C, Lerrer S, Liubomirski Y, Leider-Trejo L, Meshel T, Bar J . Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway. Stem Cell Res Ther. 2015; 6:87. PMC: 4469428. DOI: 10.1186/s13287-015-0080-7. View

Mirzaei H, Nasrollahi F, Mohammadi Yeganeh L, Jafari Naeini S, Bikdeli P, Hajian P . Dose-dense epirubicin and cyclophosphamide followed by weekly Paclitaxel in node-positive breast cancer. Chemother Res Pract. 2014; 2014:259312. PMC: 4172875. DOI: 10.1155/2014/259312. View

10.

Geyikoglu F, Colak S, Turkez H, Bakir M, Koc K, Hosseinigouzdagani M . Oleuropein Ameliorates Cisplatin-induced Hematological Damages Via Restraining Oxidative Stress and DNA Injury. Indian J Hematol Blood Transfus. 2017; 33(3):348-354. PMC: 5544628. DOI: 10.1007/s12288-016-0718-3. View

11.

Rosignoli P, Fuccelli R, Sepporta M, Fabiani R . In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil. Food Funct. 2015; 7(1):301-7. DOI: 10.1039/c5fo00932d. View

12.

Tietze F . Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969; 27(3):502-22. DOI: 10.1016/0003-2697(69)90064-5. View

13.

Shamshoum H, Vlavcheski F, Tsiani E . Anticancer effects of oleuropein. Biofactors. 2017; 43(4):517-528. DOI: 10.1002/biof.1366. View

14.

AEBI H . Catalase in vitro. Methods Enzymol. 1984; 105:121-6. DOI: 10.1016/s0076-6879(84)05016-3. View

15.

Sun W, Wang X, Hou C, Yang L, Li H, Guo J . Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Neuropharmacology. 2016; 113(Pt A):556-566. DOI: 10.1016/j.neuropharm.2016.11.010. View

16.

Jiang L, Jing C, Kong X, Li X, Ma T, Huo Q . Comparison of adjuvant ED and EC-D regimens in operable breast invasive ductal carcinoma. Oncol Lett. 2016; 12(2):1448-1454. PMC: 4950445. DOI: 10.3892/ol.2016.4754. View

17.

Li H, Hu B, Guo Z, Jiang X, Su X, Zhang X . Correlation of UGT2B7 Polymorphism with Cardiotoxicity in Breast Cancer Patients Undergoing Epirubicin/Cyclophosphamide-Docetaxel Adjuvant Chemotherapy. Yonsei Med J. 2018; 60(1):30-37. PMC: 6298890. DOI: 10.3349/ymj.2019.60.1.30. View

18.

Mahmoudi A, Ghorbel H, Bouallegui Z, Marrekchi R, Isoda H, Sayadi S . Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups'. Exp Toxicol Pathol. 2015; 67(7-8):413-25. DOI: 10.1016/j.etp.2015.04.007. View

19.

Khalili A, Nekooeian A, Khosravi M . Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes. J Asian Nat Prod Res. 2017; 19(10):1011-1021. DOI: 10.1080/10286020.2017.1307834. View

20.

Fuccelli R, Sepporta M, Rosignoli P, Morozzi G, Servili M, Fabiani R . Preventive activity of olive oil phenolic compounds on alkene epoxides induced oxidative DNA damage on human peripheral blood mononuclear cells. Nutr Cancer. 2014; 66(8):1322-30. DOI: 10.1080/01635581.2014.956251. View