The influence of curcumin and (-)-epicatechin on the genotoxicity and myelosuppression induced by etoposide in bone marrow cells of male rats

摘要

Oxidative DNA damage, caused by etoposide cytostatic drug in healthy myeloid precursors, is likely to contribute to the development of treatment-related acute myeloid leukemia (t-AML) in some cancer patients. A frequent side effect of etoposide is myelosuppression, which restricts the use of this drug. Antioxidants from the polyphenol group have the potential to limit this damage. The aim of this study was to determine the effect of (-)-epicatechin and curcumin on DNA damage and myelosuppression induced by etoposide in bone marrow cells of male rats. Rats were treated with the following: 1) (-)-epicatechin [20 and 40 mg/kg body weight (b.w.) by gavage] or curcumin (100 and 200 mg/ kg b.w. by gavage) for 7 days; 2) etoposide (50 mg/kg b.w., intraperitoneally) for 3 days; 3) (-)-epicatechin or curcumin for 4 days, followed by coadministration of etoposide for the last 3 days of the experiment; and 4) solvents of the examined compounds (control group). Bone marrow cells were isolated, and DNA damage was analyzed by comet assay. Bone marrow smears were evaluated cytologically. Etoposide administration induced serious DNA damage and hypoplasia of bone marrow. Both curcumin and (-)-epicatechin significantly attenuated etoposide-induced oxidative DNA damage. Curcumin also significantly reduced the DNA strand break and hypoplasia caused by cytostatic drug. This polyphenol increased the percentage of granulocytic precursors and lymphocytes diminished by etoposide. Curcumin exerted greater protection than (-)-epicatechin against undesirable effects induced by the cytostatic.