Pyrrolizidine alkaloid clivorine-induced oxidative stress injury in human normal liver L-02 cells.

Clivorine is an otonecine-type pyrrolizidine alkaloid isolated from the traditional Chinese medicine Ligularia hodgsonii Hook. Pyrrolizidine alkaloids (PAs) are well-known hepatotoxins widely distributed around the world. The present study sought to evaluate clivorineinduced oxidative injury in human normal liver L-02 cells. After cells were treated with various concentrations of clivorine for 48 h, cellular total antioxidant capacity, glutathione-S-transferase (GST) and glutathione reductase (GR) were determined to evaluate oxidative injury. Results showed that cellular total antioxidant capacity and GST activity both increased in clivorine-treated L-02 cells, while clivorine decreased GR activity in cells. Further, the protective effects of some antioxidants such as ascorbic acid (vitamin C, Vc), Trolox, dithiothreitol (DTT) and mannitol against clivorine-induced cytotoxicity were observed. Results showed that Trolox, which is an analogue of tocopherol (vitamin E, Ve), prevented clivorine-induced cytotoxicity in L-02 cells. Taken together, these results revealed clivorineinduced oxidative injury in human liver L-02 cells. These results also indicated the possible use of Trolox in the reduction of clivorine-induced hepatotoxicity.