Inhibition of galactosamine cytotoxicity in an in vivo/in vitro hepatocellular toxicity model

Journal Article · Tue Jun 30 04:00:00 EDT 1987 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(87)90047-0· OSTI ID:6321365

MacDonald, J R; Thayer, K J; White, C

A combined in vivo/in vitro model of galactosamine hepatotoxicity was employed to test whether previously reported cytoprotective actions of cystamine administration on galactosamine-induced hepatic injury in vivo could be attributed to a direct action of cystamine on toxicant-challenged hepatocytes. In this model, male Sprague-Dawley rats received a 400 mg/kg galactosamine challenge via intraperitoneal injection 1 hr prior to portal vein cannulation for hepatocyte isolation. Isolated cells are established in monolayer culture and galactosamine-induced cellular injury is then expressed over the ensuing 24-48 hr in culture. Consistent with the biochemical basis of galactosamine-induced hepatocellular injury in vivo, cytotoxicity could be prevented by in vitro uridine treatments within 3 hr of the in vivo galactosamine challenge, but not when added 12 hr later. Cystamine, in contrast, exhibited a cytoprotective effect even when added to cultures 12 hr after the in vivo toxicant challenge. Post-toxicant cytoprotection by cystamine in vitro was concentration dependent and did not produce an alteration of hepatocyte nonprotein sulfhydryl content. Post-toxicant cytoprotection by uridine and cystamine in this in vivo/in vitro model of toxicity were fully consistent with in vivo protection from galactosamine-induced necrosis by these agents. This model eliminates potential extrahepatic mechanisms for cystamine's hepatoprotective effect and demonstrates a direct cytoprotective action on galactosamine-challenged hepatocytes.

• Research Organization: Univ. of California, San Francisco
• OSTI ID: 6321365
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 89:2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

560152 -- Radiation Effects on Animals-- Animals
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BODY
CARBOHYDRATES
CYSTAMINE
DIGESTIVE SYSTEM
DRUGS
GLANDS
HETEROCYCLIC COMPOUNDS
HEXOSAMINES
HEXOSES
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
INHIBITION
INJURIES
LIVER
MAMMALS
MONOSACCHARIDES
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PYRIMIDINES
RADIOPROTECTIVE SUBSTANCES
RATS
RIBOSIDES
RODENTS
SACCHARIDES
TOXICITY
URACILS
URIDINE
VERTEBRATES