J. Phys. IV France 107 (2003) 1095
Involvement of intracellular Na accumulation in Hg or Cd induced cytotoxicityJ. Pourahmad1 and P.J. O'Brien2
1 Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, P.O. Box 14155-6153, Iran
2 Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario M5S 2S2, Canada
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.
© EDP Sciences 2003