Involvement of intracellular Na accumulation in Hg or Cd induced cytotoxicity

Abstract
Previously we showed that hepatocyte lysis induced by Hg ⁺² or Cd ⁺² could be partly attributed to mitochondrial toxicity [1, 2]. Similar changes in Na ⁺ homeostasis induced when Cd ⁺² or Hg ⁺² was incubated with hepatocytes. Cd ⁺² or Hg ⁺² induced cytotoxicity were prevented by Na ⁺ omission from the media or by the addition of the Na ⁺/H ⁺ exchange inhibitor 5-(N, N-dimethyl)-amiloride. Furthermore the omission of CI ^- from the media or 2 addition of glycine, a CI ^- channel blocker also prevented Cd ⁺² or Hg ⁺² induced hepatocyte toxicity. A hypotonic media also increased Cd ⁺² or Hg ⁺² induced hepatocyte cytotoxicity. This suggests that Cd ⁺² or Hg ⁺² cytotoxicity could be partly attributed to disruption of cell volume regulation mechanisms. The increased osmotic load caused by the uncontrolled accumulation of intracellular Na ⁺ in Cd ⁺² or Hg ⁺² treated hepatocytes likely resulted from the activation of Na ⁺/H ⁺ exchanger and the Na ⁺/HCO3 ^- cotransporter by the acidosis and ATP depletion caused by mitochondrial toxicity.