Targeted protection of hepatocytes from galactosamine toxicity in vivo.
| Autor: | Keegan-Rogers, Valerie, Wu, George, Keegan-Rogers, V, Wu, G Y |
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| Předmět: |
LIVER disease prevention
ALPHA fetoproteins ANIMAL behavior ANIMAL experimentation CARBOHYDRATES CELL receptors COMPARATIVE studies GLYCOPROTEINS INTRAVENOUS injections LIVER RESEARCH methodology MEDICAL cooperation NUCLEOTIDES RATS RESEARCH RESEARCH funding EVALUATION research IODINE radioisotopes CHEMICAL inhibitors |
| Zdroj: | Cancer Chemotherapy & Pharmacology; May1990, Vol. 26 Issue 2, p93-96, 4p |
| Abstrakt: | We present an in vivo model for specific protection of normal hepatocytes from damage by the highly specific hepatotoxin galactosamine. The idea is based on the fact that normal, unlike malignant, hepatocytes possess unique cell-surface receptors that can bind and internalize galactose terminal (asialo)glycoproteins by receptor-mediated endocytosis. A targetable carrier-antagonist conjugate was formed by coupling asialofetuin to the galactosamine antagonist uridine monophosphate. Intravenous injection of the antagonist conjugate resulted in specific uptake by the liver. Rats treated with carrier-antagonist conjugate together with a toxic dose of galactosamine developed significantly less hepatotoxicity than did controls. We conclude that a galactosamine antagonist can be targeted to liver, resulting in specific protection of hepatocytes from galactosamine toxicity in vivo. Because hepatoma cells lack asialoglycoprotein receptor activity, this "targeted rescue" may be of value in the differential protection of normal cells in the treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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