The role of possible membrane damage in porphyria cutanea tarda: a spin label study of rat liver cell membranes.
Two groups of rats were made porphyric by treatment for a shorter or a longer time with hexachlorobenzene (HCB); a third group was subjected to chronic treatment with ethanol; the fourth group comprised untreated, control animals. Suspensions were prepared of hepatocytes isolated from the livers of the animals in the individual groups, and in these systems the cell membranes were studied by spin labeling. In all three chronically treated groups, the order parameter calculated from the ESR spectra was significantly lower than that of the control group. The order parameters ofr the first three treated groups, however, did not differ significantly from one another. If either HCB or ethanol was incorporated into the isolated hepatocytes of the healthy control animals, the fluidity of the hepatocyte membranes increased. The order parameter decrease (compared to the control) for the hepatocyte membranes of the animals treated chronically with HCB or ethanol can be ascribed to the direct membrane-fluidizing effect of HCB or ethanol, and also to the altered lipid metabolism. With regard to the difference in the mechanisms of action of HCB and ethanol, on the basis of the experimentally proved membrane-damaging effect of the porphyrinogenic HCB it is probable that, besides other factors, the membrane damage may play an important role in the pathogenesis of porphyria cutanea tarda.