Biochemical and morphological changes in mouse liver induced by mistletoe toxins

Natural compounds are often characterized by high biological activity and sometimes toxicity. This also applies to compounds contained in the herb mistletoe. The objective of this study was to investigate short-term effects (up to 48 h) of mistletoe toxins on mouse hepatocytes. Standardized mistletoe extract Iscador P was given to female mice as a single injection (0.1 mg/kg b.w., 1 mg/kg b.w., or 2 mg/kg b.w). Activities of lysosomal hydrolases: acid phosphatase, cathepsins D and L, N-acetyl-β-D-hexosaminidase, β-D-glucuronidase, β-D-glucosidase and cytosolic proteases: arginine and leucine aminopeptidases were analyzed in the liver fractions 24 and 48 h after the injection. The morphology of hepatocytes was examined by light and transmission electron microscopy. Iscador P caused a decrease in the activity of all lysosomal hydrolases (except cathepsins) in the lysosomal pellet, and an increase in the activity of both aminopeptidases and β-D-glucuronidase in the cytosol. However, despite membranotropic properties of the viscotoxins, we did not find a significant labilising effect on the lysosomal membranes. Only β-D-glucuronidase activity was relocated to the supernatant of lysosomal fraction. Microscopic examinations revealed that hepatocyte mitochondria were enlarged and increased in number, whereas the surface of the rough endoplasmic reticulum was decreased significantly.