Cytotoxicity of D-penicillamine in association with several heavy metals against cultured rabbit articular chondrocytes

The potentiation or antagonistic effects of Cu, Hg, Pb and Cd salts in the presence of a long-acting anti-rheumatic drug, D-penicillamine (D.P.) were studied on cultured chondrocytes. CuSO₄ (10^–4M), HgCl₂ (10^–5M), Pb(CH₃COO)₂ (10^–3M) and D.P. (10^–3M) when used alone caused a small decrease in cell proliferation. The addition of D.P. with Cu, Hg or Pb salts resulted in a marked increase in the extent of growth inhibition. In contrast, CdCl₂ (10^–5M) produced an important growth inhibitory effect, and D.P. antagonized CdCl₂ action. The CuSO₄ D.P. toxicity was probably due to production of H₂O₂ in situ. To verify this hypothesis, catalase, responsible for H₂O₂ metabolism was used, and was found to partially reverse the inhibitory effect of CuSO₄-D.P.