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

Formation of reactive O-2 species in biological systems can be accomplished by copper-(II) (Cu2+) catalysis, with the consequent cytotoxic response. W e have evaluated the influence of Cu2+ On the respiratory activity of Kupff er soils in the perfused liver after colloidal carbon infusion. Studies wer e carried out in untreated rats and in animals pretreated with the Kupffer cell inactivator gadolinium chloride (GdCl3) or with the metallothionein (M T) inducing agent zinc sulphate, and results were correlated with changes i n liver sinusoidal efflux of lactate dehydrogenase (LDH) as an index of hep atotoxicity. In the concentration range of 0.1-1 mu M, Cu2+ did not modify carbon phagocytosis by Kupffer cells, whereas the carbon-induced liver O-2 uptake showed a sigmoidal-type kinetics with a half-maximal concentration o f 0.23 mu M. Carbon-induced O-2 uptake occurred concomitantly with an incre ased LDH efflux, effects that were significantly correlated and abolished b y GdCl3 pretreatment or by MT induction. It hypothesized that Cu2+ increase s Kupffer cell-dependent O-2 utilization by promotion of the free radical p rocesses related to the respiratory burst of activated liver macrophages, w hich may contribute to the concomitant development of hepatocellular injury .