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Histochemical response of mice to mistletoe lectin I (ML I)
Abstract:
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 Golgi-associated 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Mistletoe lectin ML I causes rapid liver toxicity in mice by depleting glycogen and altering enzyme activity. The ML I B chain appears less toxic than ML I A, suggesting specific components drive the toxicity.
Area of Science:
- Toxicology
- Biochemistry
- Histochemistry
Background:
- Mistletoe lectin ML I (ML I) exhibits high acute toxicity, but the underlying mechanisms remain unclear.
- Previous studies confirmed ML I's toxicity, necessitating further investigation into its cellular effects.
Purpose of the Study:
- To elucidate the toxicological mechanisms of ML I by examining its effects on various cellular components and enzymes in mice.
- To differentiate the toxic contributions of ML I A and ML I B chains.
Main Methods:
- Histochemical analysis of female mice treated with varying doses of ML I, ML I A, ML I B, or their combinations.
- Assessment of plasma membrane-associated hydrolases, ER/Golgi-linked hydrolases, oxidases, lysosomal hydrolases, dehydrogenases, cytoskeletal proteins, iron, glycogen, and lipids in all organs.
Main Results:
- ML I treatment caused complete glycogen depletion in hepatocytes, independent of dose and exposure time.
- Increased activity of Golgi-associated thiamine pyrophosphatase and non-specific alkaline phosphatase in the liver was dose- and time-dependent.
- ML I B chain alone showed minimal effects, while ML I A chain and ML I A/ML I B combinations had less impact than ML I.
Conclusions:
- ML I induces significant liver toxicity, primarily through glycogen depletion and altered enzyme activities.
- The ML I B chain appears less responsible for the observed toxicity compared to the ML I A chain or the intact ML I molecule.