Influence of copper-(II) on colloidal carbon-induced kupffer cell-dependent oxygen uptake in rat liver: Relation to hepatotoxicity

Formation of reactive O₂ species in biological systems can be accomplished by copper-(II) (Cu²⁺) catalysis, with the consequent cytotoxic response. We have evaluated the influence of Cu²⁺ on the respiratory activity of Kupffer cells in the perfused liver after colloidal carbon infusion. Studies were carried out in untreated rats and in animals pretreated with the Kupffer cell inactivator gadolinium chloride (GdCl₃) or with the metallothionein (MT) inducing agent zinc sulphate, and results were correlated with changes in liver sinusoidal efflux of lactate dehydrogenase (LDH) as an index of hepatotoxicity. In the concentration range of 0.1-1 μM, Cu²⁺ did not modify carbon phagocytosis by Kupffer cells, whereas the carbon-induced liver O₂ uptake showed a sigmoidal-type kinetics with a half-maximal concentration of 0.23 μM. Carbon-induced O₂ uptake occurred concomitantly with an increased LDH efflux, effects that were significantly correlated and abolished by GdCl₃ pretreatment or by MT induction. It is hypothesized that Cu²⁺ increases Kupffer cell-dependent O₂ utilization by promotion of the free radical processes related to the respiratory burst of activated liver macrophages, which may contribute to the concomitant development of hepatocellular injury.