Abstract： Vanadium compounds are promising therapeutic agents for the treatment of diabetes and cancer. However, vanadium toxicity has been a great concern. Many works suggested that vanadium-induced oxidative stress is a major reason of vanadium toxicity. Quercetin and green tea polyphenols （GTP） are well-known antioxidants that play important roles in the prevention of many oxidative stress-related diseases. In this study, we investigated the protective effects of quercetin and GTP against damages caused by VO（acac）2 on isolated mitochondria and whole cells. The experimental results demonstrated that quercetin and GTP could significantly inhibit mitochondrial dysfimctions induced by VO（acac）2, such as mitochondrial swelling, depolarization of the inner mitochondrial membrane potential （△ψm）, and increased release of reactive oxygen species （ROS）. Moreover, they also reduce cytotoxicity in Hep G2 cells. These results indicated that use of natural antioxidants to control the metal toxicity of vanadium compounds may be a promising strategy for developing metal-based therapeutic agents.
Gd3＋ complexes have a variety of medical applications.In order to shed light on the mechanism of hepatotoxicity of Gd3＋ compounds,we investigated the effects of GdCl3 on human embryo liver cell strand （L02 cells）.The experimental results showed that long-time exposure to GdCl3 resulted in L02 cell apoptosis.The incubation of L02 cells with GdCl3 first induced increase in cellular reactive oxygen species （ROS） and decrease in mitochondrial inner membrane potential （？ψm）.It later resulted in the activation of poly （ADP-ribose） polymerase （PARP） and the release of mitochondrial apoptosis-inducing factor （AIF）.The activation of caspase 3,however,was not observed.Antioxidants could significantly reduce GdCl3-induced decrease of Δψm,release of AIF,and cell apoptosis.Although GdCl3 caused a significant increase in cell membrane permeability in L02,the change of cell membrane permeability was unlikely to be involved in GdCl3-induced cell apoptosis.Overall,our experimental results suggested that GdCl3 induced apoptosis of human embryo liver L02 cell line by ROS-mediated AIF pathway.
