45Calcium uptake during the transition from reversible to irreversible liver injury induced by D-galactosamine in vivo.
The hepatic uptake of 45calcium (45Ca) was studied in rats after administration of D-galactosamine (3 mmoles per kg, i.v.). In contrast to measurements of the hepatic calcium content, 45Ca uptake served as a dynamic rather than a static indicator of calcium homeostasis during the transition from reversible to irreversible liver injury which occurs between 3 and 4 hr after injection of the hepatotoxin. 45Ca uptake during a 1 hr-labeling period increased from 25 to 100% above control between 3 and 4 hr and subsequently remained at this level. The rise in 45Ca uptake and in hepatic calcium content occurred 2 to 3 hr after the D-galactosamine-induced depletion of UTP, UDP-galactose, UDP-glucose and UDP-glucuronate. The level of UDP-glucuronate was the earliest to recover. The enhanced 45Ca uptake was associated with hepatic glycogen breakdown and with an increased SGPT activity in plasma. Inhibition of RNA polymerase II by alpha-amanitin (0.5 mg per kg, i.p.) and of dolichol-dependent protein glycosylation as well as ganglioside synthesis by tunicamycin (2 mg per kg, i.p.) were used to imitate two of the early actions of D-galactosamine and indicated that an interference with either process can lead to an enhanced uptake of 45Ca into the liver in vivo. Uridine, at a dose replenishing uracil nucleotide pools after their depletion by D-galactosamine, prevented or reversed the rise in 45Ca uptake. The antiinflammatory steroid dexamethasone, injected prior to or simultaneously with D-galactosamine also protected against the loss of calcium homeostasis and the development of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)
D000410:Alanine Transaminase / Q000097:blood; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000517:prevention & control; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D006706:Homeostasis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014415:Tunicamycin / Q000494:pharmacology; D014529:Uridine / Q000494:pharmacology; D014531:Uridine Diphosphate Galactose / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism
D000546:Amanitins; D002132:Calcium Radioisotopes; D008112:Liver Glycogen; D014415:Tunicamycin; D014535:Uridine Diphosphate Glucuronic Acid; D014531:Uridine Diphosphate Galactose; D012313:RNA; D005688:Galactosamine; D003907:Dexamethasone; D000410:Alanine Transaminase; D002118:Calcium; D014544:Uridine Triphosphate; D014532:Uridine Diphosphate Glucose; D014529:Uridine