Diminished serum Gc (vitamin D-binding protein) levels and increased Gc:G-actin complexes in a hamster model of fulminant hepatic necrosis.
Evidence for increased plasma levels of complexes containing Gc (vitamin D-binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three-step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodiffusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster-acetaminophen hepatotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue necrosis.
D000082:Acetaminophen; D000199:Actins / Q000097:blood* / Q000502:physiology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D006224:Cricetinae; D006706:Homeostasis; D005779:Immunodiffusion; D007122:Immunoelectrophoresis; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008647:Mesocricetus; D009336:Necrosis; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000502:physiology
D000199:Actins; D014809:Vitamin D-Binding Protein; D000082:Acetaminophen; D001219:Aspartate Aminotransferases