Differential effects of salen and manganese-salen complex (EUK-8) on the regulation of cellular cadmium uptake and toxicity

Cadmium (Cd) stimulates the production of reactive oxygen species (ROS) and causes cell damage. We investigated here the feasibility of using a cell permeable superoxide dismutase/catalase mimetic, EUK-8, to reduce the Cd-induced ROS and cytotoxicity in Chinese hamster ovary cells. EUK-8 reduces the ROS level caused by Cd treatment. EUK-8 also curtails propidium iodide (PI) influx and increases the viability of Cd-treated cells. The efficacy of EUK-8 as a Cd antidote diminishes gradually when added at a later stage of Cd treatment. EUK-8 blocks Cd transport into cells. It is ineffective in accelerating the efflux of metals from the cells. EUK-8 is a Mn-salen complex. Mn decreases the uptake and cytotoxicity of Cd, while salen perturbs the membrane integrity and increases the uptake and cytotoxicity of Cd. Salen is able to bind Cd, and the Cd-salen complex formed does not perturb the integrity of cell membranes and thus the influx of metal is not enhanced. Our results reveal a differential effect of salen and Mn-salen complex on the transport of Cd with subsequent different levels of cell damage.