Effects of C60, a fullerene, on the activities of glutathione S-transferase and glutathione-related enzymes in rodent and human livers

The effects of C-60, a fullerene, on the activities of glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in rodent and human livers were investigated. The GST activity in rat liver towards trans-4-phenyl-3-buten-2-one and that in mouse liver towards ethacrynic acid were inhibited by C-60. The GST activity towards 1,2-dichloro-4-nitrobenzene, isomerase activity of GST towards androst-5-ene-3,17-dione, GSH-Px activity and GR activity were not affected by C-60. A kinetic study using purified mouse GST-a with ethacrynic acid (25-100 mu M) as the substrate revealed that C-60 was a non-competitive inhibitor of the enzyme with a K-i = 48.8 +/- 0.25 mu M and a K-i' = 47.9 +/- 0.18 mu M. However, C-60 did not inhibit the activity of purified mouse GST-pi towards 1-chloro-2,4-dinitrobenzene. Thus, the inhibition by C-60 appears to be substrate-specific. In human liver, C-60 inhibited the GST activity towards ethacrynic acid, and moderately inhibited GSH-Px and GR activities.