J. Phys. IV France 107 (2003) 1091
Contribution of Ca ions influx in Cu (II) or Cr (VI) induced hepatocyte 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 Cu (II) or Cr (VI) could be partly attributed to membrane lipid peroxidation induced by Cu (II) or Cr (VI) [1, 2]. Changes in Na + and Ca +2 homeostasis induced when Cu +2 or Cr VI were incubated with hepatocytes. Na + omission from the media or addition of the Na +/H + exchange inhibitor 5-(N, N-dimethyl)-amiloride markedly increased Cu (II) or Cr (VI) cytotoxicity even though Cu (II) or Cr (VI) did not increase hepatocyte Na + when the media contained Na +. The omission of CI - from the media or addition of glycine, a CI - channel blocker also enhanced Cu (II) or Cr (VI) induced cytotoxicity. Intracellular Ca +2 levels however were markedly increased when the hepatocytes were incubated with Cu +2 or Cr VI in a Na + free media and removing media Ca +2 with EGTA also prevented Cu (II) or Cr (VI) induced hepatocyte cytotoxicity. This suggests that intracellular Ca +2 accumulation contributes to Cu (II) or Cr (VI) induced cytotoxicity and a Na +- dependent Ca +2 transporter is involved in controlling excessive Ca +2 accumulation caused by Cu (II) or Cr (VI).
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