Subcellular distribution of hepatic copper, zinc and iron and serum ceruloplasmin in rats intoxicated by oral pyrrolizidine (Senecio) alkaloids.

Pair-fed rats were given diets containing 250 ppm added Cu with or without 5% Senecio jacobaea (S J), a poisonous plant containing the highly toxic pyrrolizidine alkaloids (PA). Levels of Cu, Zn and Fe were determined in whole liver, kidney, spleen, serum and subcellular fractions of liver. Serum ceruloplasmin and hematocrit values were also obtained. At 5 wk, a 7.5-fold increase in liver Cu was observed for the S J-treated rats when compared with controls (P<.O1). Percentage distribution of total Cu was greater in the nuclei and debris fraction (P<.O01) and reduced in the lysosomal and cytosolic fractions (P<.05) as a response to PA intoxication caused by SJ. Liver Zn was decreased (P<.05) as a result of SJ consumption; however, alterations in distribution of Zn among the fractions were not significant. The SJ caused an increase in liver Fe levels (P<.01) with the cytosol fraction showing the only significant increase. Ingestion of SJ also caused increased spleen weight (P<.O01), spleen Cu level (P<.05), kidney weight (P<.01) and kidney Cu level (P<.01). Mean hematocrit was not different (P>.05), between treatments, but more variation was observed as a result of SJ consumption. Consumption of SJ also resulted in elevated activity of serum ceruloplasmin (P<.01) and serum Cu (P<.05). Higher levels of Cu in the nuclei and debris suggest impairment or saturation of normal subcellular excretory mechanisms and may involve a lysosomal defect. The increased hepatic Fe, hematocrit