Anti-endotoxin actions of methylprednisolone in the isolated perfused cat liver. 1978

M J Galvin, and K Shupe, and A M Lefer

The efficacy of the synthetic glucocorticoid, methylprednisolone, was examined in vitro using an isolated cat liver perfused with a blood-free medium. Addition of endotoxin (75 microgram/g tissue) to the perfusate did not change perfusion pressure or total oxygen consumption. However, cellular integrity was severely compromised as reflected by increases in perfusate lactate dehydrogenase and cathepsin D activities, increases in tissue lysosomal fragility, and enlargement and vacuolization of lysosomes. Addition of methylprednisolone (1 x 10(-3) M) to the perfusion medium prevented the endotoxin-induced changes in hepatocyte integrity. It is suggested that a major action of endotoxin in the liver is to increase lysosomal fragility, and the protective action of methylprednisolone appears to be related to its lysosomal stabilizing action. The potent anti-endotoxin action of glucocorticoids in vivo may be due in part to the stabilization of lysosomal membranes in tissues such as the liver.

UI MeSH Term Description Entries
D007770 L-Lactate Dehydrogenase A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008297 Male Males
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D002403 Cathepsins A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES. Cathepsin
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D005260 Female Females

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