GALACTOSAMINE-INDUCED CELL-DEATH IN PRIMARY CULTURES OF RAT HEPATOCYTES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 100  (1) , 25-38
Abstract
Primary cultures of rat hepatocytes were exposed to 0.5 mM D-galactosamine. After 36 h, only 10-20% of the original cells were viable, as assessed by trypan blue exclusion. In the absence of galactosamine, there was no loss of viability over this same period. The addition of 3 mM uridine to the culture medium completely prevented the cell death produced by galactosamine. Glucosamine had no effect on the viability of the hepatocytes. The extent of galactosamine-induced cell death was dependent upon the concentration of Ca2+ ions in the culture medium. With the only source of Ca2+ that added with the fetal calf serum, galactosamine had only a very slight effect on viability. With higher Ca2+ than with the fetal calf serum, galactosamine had only a very slight effect on viability. With higher Ca2+ concentrations, from 0.9-3.6 mM, the viability ranged from 75-31% 18 h after treatment with galactosamine. The addition of 1.4 .mu.M chlorpromazine to culture medium containing 1.8 mM Ca2+ decreased the extent of the galactosamine-induced cell death. This protective effect was progressively reduced by raising the Ca2+ concentration to 3.6 and 5.4 mM. Chlorpromazine given to intact rats 2 h after treatment with 400 mg/kg galactosamine prevented the appearance of liver cell necrosis. At the same time, chlorpromazine prevented the increases in liver cell Ca2+ content. Apparently, many of the features of the effect of galactosamine on intact rat liver cells can be reproduced in primary cultures of these same cells. A disturbance in intracellular Ca2+ homeostasis leading to accumulations of these ions is causally related to the cell death produced by galactosamine.

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