Effects of Oleuropein on Epirubicin and Cyclophosphamide Combination Treatment in Rats

Abstract

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 in vitro and in vivo studies. This study aimed to explore the effects of oleuropein on cyclophosphamideand epirubicin-induced toxicity in female rats. 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. 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. 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.