SEMPERVIVUM MARMOREUM EXTRACT MODULATES THE CLASTOGENIC EFFECT OF CYTOSTATIC CCNU ON RAT NUCLEATED BLOOD CELLS
Abstract:
Identification of chemical agents reducing the unwanted clastogenic side effects of cytostatics on normal cells is a major objective in the progress of the modern chemotherapy. Sempervivum marmoreum Griseb. is a monocarpic perennial Crassulaceaean, native in dry habitats in rocky zones. Previous experiments demonstrated antioxidant and anti-inflammatory properties of Sempervivum sp. extracts on various experimental models, suggesting a hematoprotector potential in clastogenic chemotherapy. Based on existing data regarding the pharmacological activity of Sempervivum spp and on metabolism-phylogeny correlation, we consider that Sempervivum marmoreum extract (SEMEX) should have anticlastogenic activity,-modulating the effect of the alkylant cytostatics. We hereby report the evaluation the modulatory effect of SEMEX on the DNA fragmentation in rat nucleated blood cells, with the scope of its use as adjuvant in the chemotherapy with CCNU (=N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea ) – cytostatic finally producing DNA DSBs. Wistar rats were treated with CCNU and/or 3 concentrations (25%, 50%, 100%) of total extracts obtained from cultivated S. marmoreum; DNA fragmentation in nucleated blood cells was evaluated by PFGE-CHEF technique. Densitometric analysis of the DNA electrophoretic migration in the treatments clearly shows the following effects: 1-Consistent modification the DNA fragmentation profiles under the action of cytostatic, after the SEMEX administration; 2- Doze-dependence of the modulation intensity of (Deoxyribonucleic acid) DNA fragmentation. 3 - Evidence of a surprising intrinsic clastogenic effect of SEMEX administered alone. The densitometric profiles with different distribution of density maxima suggest a protective effect of SEMEX against the clastogenic activity of CCNU, decreasing DSB number and/or increasing of the postclastic DNA-repair efficiency
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