Genotoxicity and cytotoxicity evaluation of oenothein B and its protective effect against mitomycin C-induced mutagenic action.

The natural product oenothein B (OeB), a dimeric macrocyclic ellagitannin, has a wide range of biological activities, such as antioxidant, anti-inflammatory, anti-viral, antifungal, and antitumor. However, investigations concerning its genotoxicity have not been carried out. This study assessed the cytotoxicity, genotoxicity, and protective effects of oenothein B using in vitro SOS-Inductest and in vivo mouse bone marrow micronucleus (MN) assay through oral and intraperitonial routes. In both assays oenothein B did not produce genotoxic effects in any of doses tested; in contrast, cytotoxic effect in cells was detected only in mice groups treated by both routes and exposed for 24 and 48h. Antigenotoxic and anticytotoxic activities of oenothein B were evaluated using both assays in combination with mitomycin C (MMC), a bioreductive alkylating agent. In the MN assay, a significant reduction was observed in MN frequency in all groups co-treated with MMC and OeB compared to those which received only MMC. Anticytotoxicity was observed in mice groups exposed to OeB and MMC for 24 and 48h. In the SOS-Inductest, oenothein B failed to show antigenotoxic and anticytotoxic effects; thus, it undoubtedly showed an in vivo protective activity against primary DNA damage induced by mitomycin C.