ABSTRACT
BACKGROUND: An extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids. RESULTS: From the ethyl acetate fraction obtained from fractionation of the methanol extract of S. suberectus Dunn, medicarpin, formononetin and isoliquiritigenin were successfully isolated through a combination of normal- and reversed-phase chromatography. Genistein and naringenin, which were already reported to be contained in S. suberectus Dunn, were also tested for their antimutagenicity towards MNU, along with formononetin, isoliquiritigenin and medicarpin. Our results demonstrated that genistein, isoliquiritigenin, medicarpin and naringenin were antimutagenic against MNU without showing cytotoxicity. MNU is reported to cause not only DNA alkylation but also induce reactive oxygen species. The hydroxyl radical scavenging capacity of the flavonoids was correlated with the antimutagenic capacity, indicating that the hydroxyl radical scavenging activity was involved in their antimutagenicity towards MNU. CONCLUSIONS: It is important to prevent DNA damage by N-nitrosamines for cancer chemoprevention. Genistein, isoliquiritigenin, medicarpin and naringenin were demonstrated to possess an antigenotoxic effects against carcinogenic MNU due to their radical scavenging activity.
ABSTRACT
Exposure to air pollution containing diesel exhaust particles (DEP) is associated with an increase in mortality rate attributed to cardiovascular diseases, but the mechanisms by which DEP produces adverse cardiovascular effects at the cellular level are not elucidated. This study investigated the cytotoxic mechanisms underlying DEP-induced neonatal rat cardiac myocytes effects in vitro, focusing on the role of reactive oxygen species (ROS). DEP extracts (DEPE) damaged cells in a concentration- and a time-dependent manner. Lactate dehydrogenase activity leaked to medium was also increased in a concentration-dependent manner after 24 h of DEPE exposure. DEPE-induced cytotoxicity was markedly reduced by treatment with superoxide dismutase, catalase, and N-(2-mercaptopropionyl)-glycine. Furthermore, superoxide was produced from both DEPE and myocardial cells. These results suggest that ROS such as superoxide, hydrogen peroxide, and hydroxyl radical are involved in DEPE-induced cardiac cell damage.
