Effect of cutaneous human or mouse burn toxin on the metabolic function of isolated liver cells

Studies on isolated perfused rat livers 5 days after either a sublethal burn or an i.p. injection of human/mouse burn toxin showed a significant inhibition of the glucose/urea synthesis and the ATP production concomitantly with ultrastructural mitochondrial damages. A direct specific effect of these burn toxins on enzymatically isolated liver parenchyma cells was found either after direct incubation of the isolated cells with the compound or 5 days after injection of the toxin to the animals followed by the isolation of the cells. Control experiments were performed with the "native" non-toxic precursor from normal skin. Liver cells of rats pretreated with the toxin showed an 100% increase of the amino-acid release while this increase was 70% after direct toxin incubation. Glycogen synthesis from lactate, alanin and fructose was significantly decreased in both toxin groups while the glucose synthesis was not altered. The degree of the inhibition of the glycogen synthesis was directly correlated to the number of ATP-dependent metabolic steps. A disturbance of the oxygen transfer system by structural damages of the mitochondria seems to be the basic mechanism for these specific metabolic alterations due to ultrastructural mitochondrial damages.