The protective effect of oleuropein against radiation-induced cytotoxicity, apoptosis and genetic damage in cultured human lymphocytes.

Purpose: Oleuropein is one of the most abundant and important phenolic compounds in fruits and olive leaves . In this research, the radioprotective effect of oleuropein was investigated versus 2 Gy of gamma radiation on human peripheral blood mononuclear cells. The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector.Materials and Method: Human mononuclear cells were treated with oleuropein at the concentration of 100 μM (optimum concentration), incubated for 24 hours, and then exposed to 2Gy gamma rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay.Results: It was found that pre-treatment with oleuropein (25, 50, 75, 100, 200, 400, and 800 nM -1, 5, 10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, 175, 200 µM) significantly increased the percentage of cell viability compared to the irradiated group (p < 0.001) . Moreover, oleuropein treatment with the above concentrations defined without γ-ray did not show any cytotoxicity effect in human mononuclear cells . The LD 50/24h dose was calculated as 2.9 Gy, whereas by 200, 150, 50, and 100 µM oleuropein prior to radiation (1, 2,and 4 Gy) , radiation LD 50/24h increased to 3.36, 3.54, 3.81, and greater than 4 Gy, in that order. A very noticeable dose-modifying factor (DMF) of 1.16, 1.23, 1.31, and 1.72 was observed for 200, 150, 50, and 100µM, in order . Therefore, 100 µM of oleuropein was selected as the desirable dose for radio-protection trial, and 2 Gy gamma rays were used for further research . Human mononuclear cells treatment with oleuropein (100 µM) prior to 2Gy gamma rays significantly decreased apoptosis, genomic damage, and MN occurrence in human mononuclear caused by γ-radiation (p < 0.001) . Further more, treatment with oleuropein (100 µM) without radiation did not lead to apoptosis, genotoxicity, or clastogenic effects caused by oleuropein in human mononuclear cells.Conclusion: The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genotoxic, and clastogenic effects of gamma rays.