Possible role of ca²⁺ in heavy metal cytotoxicity

1. 1. Organic xenobiotic metabolism often results in oxidative stress, involving GSH depletion, alteration of thiol/disulphide balance and peroxidation of membrane lipids. These events can lead to the disruption of Ca²⁺ homeostasis, through impairment of the Ca²⁺ translocases present in cellular membranes. Inhibition of the activity of Ca,Mg-ATPases due to oxidation of their SH groups would lead to uncontrolled rises in cytosolic Ca²⁺ levels resulting in loss of cell viability. 2. 2. These observations seem to be of interest when interpreting the biochemical mechanisms of heavy metal cytotoxicity. Since these cations (such as Hg²⁺, Cu²⁺, Cd²⁺ and Zn) have an extremely high affinity for SH groups, they may affect the function of SH containing proteins, such as the Ca,Mg-ATPases, as in the case of oxidative stress. 3. 3. Results are reported indicating that Hg²⁺ may stimulate Ca²⁺ influx through voltage-dependent channels in different experimental systems. Moreover, evidence is presented that heavy metals can inhibit Ca,Mg-ATPase activity and affect mitochondrial functions in the cells of different organisms. 4. 4. The possibility that heavy metal cytotoxicity is mediated through disruption of Ca²⁺ homeostasis is discussed.