Spermine stimulation of CCl4 depressed protein synthesis in rabbits.

CCl4, 2.5 ml/kg body weight, was administered via a gastric tube to fed rabbits 2 hr before the livers were removed and perfused. Electron microscope studies of the liver showed that CCl4 caused a decrease in the rough endoplasmic reticulum and an increase in the smooth reticulum. The reticulum was dilated and vesiculated with few attached ribosomes. Sucrose gradient analysis of the endoplasmic reticulum bound polysomes showed them to be considerably disaggreated, and albumin synthesis and 14C-incorporation into proteins secreted into the perfusate were decreased. These effects were partially reversed when these livers were perfused with either 1 mM spermine of 10 mM arginine. Perfusion with both arginine and spermine increased endoplasmic reticulum bound polysome aggregation to about 92% of control and albumin synthesis increased from a low of 3.3 mg/100 g wet liver weight to 8.2 mg/hr or 37% of control. 14C-Incorporation into total hepatic protein and secretory proteins increased as well. The combination of spermine and arginine was more effective in stimulating albumin synthesis than either agent alone. The ability of spermine to partially reverse a specific toxic effect of carbon tetracholoride, namely polysome disaggregation, and to stimulate protein production is noted.