Histochemical response of mice to mistletoe lectin I (ML I)

Summary

The acute toxicity of lectin ML I from the toxic drug, mistletoe, was demonstrated in previous experiments. Because the reason for this extremely high toxicity is not yet clear, mice were studied histochemically at different times after treatment with various doses of ML I, ML I A or ML I B chain separately, or recombinations of ML I A and ML I B. Various plasma membrane-associated hydrolases as well as Golgi apparatus-and endoplasmic reticulum-linked hydrolases, peroxisomal and extraperoxisomal oxidases, lysosomal hydrolases, mitochondrial dehydrogenases, the cytoskeletal proteins keratin and vimentin as well as iron, glycogen and lipids were analysed in all organs and tissues of female mice. Irrespective of the dose, a clear-cut response was only observed in the liver. After ML I treatment, glycogen disappeared completely from all hepatocytes, and this effect did not depend on the ML I-concentration and exposure time. The increase in activity of Golgiassociated thiamine pyrophosphatase in hepatocytes and of non-specific alkaline phosphatase in the sinusoidal endothelial cells depended on the applied ML I concentration and the time of treatment. Doses of 600 or 900 ng ML I/kg drastically increased the phosphatase activities. These clear-cut changes of glycogen and enzyme activities were not observed after administration of the ML I B chain alone, and less so when the mice were treated only with the ML I A chain, or were treated with a recombination of ML I A and ML I B even at concentrations higher than that of ML I. The glycogen as well as thiamine pyrophosphatase and non-specific alkaline phosphatase responses after ML I administration were highly reproducible. None of the other investigated cell constituents responded to treatment with ML I, irrespective of the organs, tissues and cells analysed. This was also true for mice treated with ML I concentrations higher than the LD₅₀, after which the animals died with 2–3 days. In conclusion, application of ML I induces clear-cut liver cell changes, which are not observed after treatment with individual constituents of the ML I molecule either singly or in recombination. However, these changes do not explain the deaths of the animals.