Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1995-11-9
pubmed:abstractText
Dogs are particularly susceptible to development of glucocorticoid-induced hepatopathy, but the mechanisms are not well understood. We investigated the pathogenesis of glucocorticoid hepatopathy by examining sequential morphologic and biochemical changes in the liver of dogs during steroid administration. Six adult Beagles were given prednisolone acetate (4mg/kg of body weight, once daily for 24 days IM). Serum samples and percutaneous liver biopsy specimens were obtained before the start of the study (treatment day [TD] 0) and at TD 5, 10, 15, and 25. There were significant (P < 0.05) and progressive increases in serum activities of alkaline phosphatase, gamma-glutamyltransferase, and alanine transaminase. Light microscopic changes in liver biopsy specimens included progressive hepatocellular swelling and vacuolation. Electron microscopy revealed glycogen accumulation, peripheral displacement of organelles, and prominent dilatation of bile canaliculi, compared with findings at TD 0. Liver biopsy specimens taken at TD 25 had significantly (P < 0.05) increased activities of the plasma membrane enzymes, alkaline phosphatase and gamma-glutamyltransferase, and 5'-nucleotidase was significantly (P < 0.001) decreased. Subcellular fractionation on reorientating sucrose density gradients revealed high-density peaks of alkaline phosphatase and gamma-glutamyltransferase, compatible with a specific increase in the biliary canalicular component of the enzyme activities. Neutral alpha-glucosidase activity was shifted to the denser fractions, indicative of an increase in the proportion of rough to smooth endoplasmic reticulum and consistent with enhanced synthesis of plasma membrane proteins. There also was evidence for progressive increase in fragility of intracellular organelles, particularly lysosomes. These findings indicate that glucocorticoid hepatopathy in dogs is associated with progressive alterations not only to the plasma membrane, but also to other subcellular organelles.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0002-9645
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
898-907
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed-meshheading:7574158-Alanine Transaminase, pubmed-meshheading:7574158-Alkaline Phosphatase, pubmed-meshheading:7574158-Animals, pubmed-meshheading:7574158-Aspartate Aminotransferases, pubmed-meshheading:7574158-Biological Markers, pubmed-meshheading:7574158-Biopsy, pubmed-meshheading:7574158-Cell Membrane, pubmed-meshheading:7574158-Dogs, pubmed-meshheading:7574158-Female, pubmed-meshheading:7574158-Liver, pubmed-meshheading:7574158-Liver Function Tests, pubmed-meshheading:7574158-Male, pubmed-meshheading:7574158-Microscopy, Electron, pubmed-meshheading:7574158-Organelles, pubmed-meshheading:7574158-Prednisolone, pubmed-meshheading:7574158-Reference Values, pubmed-meshheading:7574158-Subcellular Fractions, pubmed-meshheading:7574158-Time Factors, pubmed-meshheading:7574158-gamma-Glutamyltransferase
pubmed:year
1995
pubmed:articleTitle
Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs.
pubmed:affiliation
Department of Small Animal Medicine and Surgery, Royal Veterinary College, University of London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't