Amavadin is a natural vanadium compound that accumulates to high level in poisonous Amanita mushrooms. Recently, amavadin was found to have potential therapeutic effect in cancer treatment. However, its toxicity and the possible mechanism of actions are still not clear. In this study, we investigated the toxic effects of amavadin on rat kidney mitochondria and the possible mechanism. We found that amavadin induced significantly permeability transition pore （PTP） opening in the mitochondria. Amavadin y inhibited the generation of reactive oxygen species （ROS） in succinate buffer, and at high concentration of 200 gM it increased the ROS generation in malate buffer. With the addition of rotenone, the ROS generation in malate buffer was strongly enhanced than that induced by amavadin alone, but remained unchanged in succinate buffer. Results from the present study suggest that amavadin act upon electron transport chain downstream of rotenone, and the ubiquinone binding site in complex I is the most possible binding site.
