The interaction of the orthopaedic metals, chromium VI and nickel, with hepatocytes.

High levels of metal ions, such as chromium and nickel, released from metallic total hip implants have been detected in the serum and urine of patients. Cr VI and Ni ions are carcinogenic and toxic and there is concern about their systemic toxicity. To investigate this we have studied the interaction of Cr VI and Ni with hepatocytes. Both metal ions caused loss of cell viability within 3 h exposure, Cr VI was more potent than Ni. Cr VI caused depletion of intracellular reduced glutathione (GSH) levels, and inhibition of glutathione reductase and glutathione-S-transferase (GST) activities. Expression of alpha-GST, the major isoenzyme of GST in rat liver, was also decreased by Cr VI. Ni, on the other hand did not deplete GSH, or inhibit any of the enzyme activities measured in the cells. GSH and GST form a major protection and detoxification system in the liver, and depletion of GSH and inhibition of GST activity by Cr VI in vivo may severely compromise the ability of an individual to protect himself against carcinogenic and cytotoxic chemicals in the environment.