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 microM, 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 microM. 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.
Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago.
J
J
Sans
A M
AM
Aguilera
P
P
Faundez
P
P
Troncoso
V
V
Fernandez
L A
LA
Videla
D000818:Animals; D002244:Carbon / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005682:Gadolinium / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000032:analysis; D010101:Oxygen Consumption; D010477:Perfusion; D010587:Phagocytosis / Q000187:drug effects; D011205:Povidone / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst; D019287:Zinc Sulfate / Q000494:pharmacology
D004338:Drug Combinations; C078073:carbon colloid; D002244:Carbon; D019287:Zinc Sulfate; D003300:Copper; D008668:Metallothionein; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D011205:Povidone; D005978:Glutathione; C038958:gadolinium chloride