Cytotoxic Effects of Hydroxylated Fullerenes in Three Types of Liver Cells

Kumiko Shimizu; Reiji Kubota; Norihiro Kobayashi; Maiko Tahara; Naoki Sugimoto; Tetsuji Nishimura; Yoshiaki Ikarashi

doi:10.3390/ma6072713

Cytotoxic Effects of Hydroxylated Fullerenes in Three Types of Liver Cells

Materials (Basel). 2013 Jul 9;6(7):2713-2722. doi: 10.3390/ma6072713.

Authors

Kumiko Shimizu¹, Reiji Kubota², Norihiro Kobayashi³, Maiko Tahara⁴, Naoki Sugimoto⁵, Tetsuji Nishimura^{6

7}, Yoshiaki Ikarashi⁸

Affiliations

¹ Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. kshimizu@nihs.go.jp.
² Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. reijik@nihs.go.jp.
³ Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. norihiro.kobayashi@nihs.go.jp.
⁴ Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. tahara@nihs.go.jp.
⁵ Division of Food Additives, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. nsugimot@nihs.go.jp.
⁶ Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. t.nishimura@thu.ac.jp.
⁷ Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Uruidominami 4-1, Ichihara-shi, Chiba 290-0193, Japan. t.nishimura@thu.ac.jp.
⁸ Division of Environmental Chemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. ikarashi@nihs.go.jp.

Abstract

Fullerenes C₆₀ have attracted considerable attention in the biomedical field due to their interesting properties. Although there has been a concern that C₆₀ could be metabolized to hydroxylated fullerenes (C₆₀(OH)_x) in vivo, there is little information on the effect of hydroxylated C₆₀ on liver cells. In the present study, we evaluated the cytotoxic effects of fullerene C₆₀ and various hydroxylated C₆₀ derivatives, C₆₀(OH)₂, C₆₀(OH)_6-12, C₆₀(OH)₁₂ and C₆₀(OH)₃₆, with three different types of liver cells, dRLh-84, HepG2 and primary cultured rat hepatocytes. C₆₀, C₆₀(OH)₂ and C₆₀(OH)₃₆ exhibited little or no cytotoxicity in all of the cell types, while C₆₀(OH)_6-12 and C₆₀(OH)₁₂ induced cytotoxic effects in dRLh-84 cells, accompanied by the appearance of numerous vacuoles around the nucleus. Moreover, mitochondrial activity in liver cells was significantly inhibited by C₆₀(OH)_6-12 and C₆₀(OH)₁₂. These results indicate that the number of hydroxyl groups on C₆₀(OH)_x contribute to the difference of their cytotoxic potential and mitochondrial damage in liver cells.

Keywords: C60; cytotoxic activity; hydroxylated fullerene; liver cells; mitochondrial damage.