Biol. Pharm. Bull. 28(2) 253—259 (2005)

uitously found in plants. Fruits and vegetables, as well as popular beverages such as wine, tea, and coffee, are the main dietary sources of flavonoids. It has been reported that flavonoids show pharmacological effects such as antioxidant, antiviral, antitumor, and antiinflammatory activities. In particular, their antioxidant activity has attracted much attention as a possible dietary preventive against cardiovascular and neurodegenerative diseases. There are many reports that flavonoids act as antioxidants and protect various cell types from oxidative stress-mediated cell injury. We reported that flavonoids have protective effects on human umbilical vein endothelial (HUVE) cells and rat neuronal cells (PC12) exposed to the highly toxic lipid peroxide linoleic acid hydroperoxide. In addition, it has been observed that flavonoids suppress the cytotoxicity of hydrogen peroxide toward Chinese hamster cells (V79) and oxidized low-density lipoproteins in human lymphoid cell lines, glucose oxidase-mediated apoptosis in mouse thymocytes, and metal-induced lipid hydroperoxide-dependent lipid peroxidation in a-linoleic acid-loaded rat hepatocytes. On the other hand, it has been suggested that flavonoids act as mutagens, prooxidants, and enzyme inhibitors. Further, it has been reported that they exert cytotoxicity at higher concentrations and in the presence of oxidation-catalyzing factors such as transition metal ions. The cytotoxicity of flavonoids toward human promyelocytic leukemia cells (HL60), human acute myelogeneous leukemia cells (KG1, KG1a, THP-1, and U937), rhesus monkey kidney cells (LLC-MK2), rat glial tumor cells (C6), bovine leukemia virus-transformed lamb embryo kidney fibroblasts (FLK), mouse and hamster pancreatic b-cells (b TC1 and HIT), human fibroblasts (HFK-2), human keratinocytes (HaCaT), human breast cancer adenocarcinoma cells (MCF-7), human neuroblastoma cells (SHEP and WAC-2), and bovine capillary endothelial cells has been found. As shown above, however, there are only a few reports on the cytotoxicity of flavonoids toward human normal cells. If flavonoids are used as dietary factors for health maintenance, relatively large amounts may be ingested. Thus the potentially toxic effects of excessive flavonoid intake must be clarified. In the present paper, we describe the cytotoxicity of nine flavonoids, including the two flavones apigenin and luteolin, the three flavonols 3-hydroxyflavone, kaempherol, and quercetin, the flavonol glycoside rutin, the two flavanones eriodictyol and naringenin, and the flavanol taxifolin (Table 1 and Fig. 1), toward cultured normal human cells, TIG-1 cells and HUVE cells. Further, we examined the intracellular levels of ROS in flavonoid-treated TIG-1 cells using DCF-DA and their incorporation of flavonoids in culture medium. February 2005 Biol. Pharm. Bull. 28(2) 253—259 (2005) 253