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Spermine stimulation of CCl4 depressed protein synthesis in rabbits
Abstract:
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.
Insights
Carbon tetrachloride (CCl4) liver damage disrupts protein synthesis by disaggregating polysomes. Spermine and arginine combination effectively reverses this damage, restoring albumin synthesis in rabbit livers.
Area of Science:
- Hepatology
- Toxicology
- Biochemistry
Background:
- Carbon tetrachloride (CCl4) is a known hepatotoxin.
- CCl4 exposure causes significant cellular damage in the liver, affecting protein synthesis machinery.
Purpose of the Study:
- To investigate the effects of CCl4 on liver endoplasmic reticulum and polysome structure.
- To evaluate the potential of spermine and arginine in reversing CCl4-induced liver damage and impaired protein synthesis.
Main Methods:
- Administration of CCl4 to rabbits followed by liver perfusion.
- Electron microscopy to assess endoplasmic reticulum morphology.
- Sucrose gradient analysis to evaluate polysome aggregation.
- Measurement of albumin synthesis and protein incorporation using 14C.
Main Results:
- CCl4 caused endoplasmic reticulum dilation, reduced rough ER, and polysome disaggregation.
- Albumin synthesis and protein secretion were significantly decreased post-CCl4 exposure.
- Perfusion with spermine or arginine partially reversed these effects.
- Combined spermine and arginine treatment restored polysome aggregation to 92% of control and significantly increased albumin synthesis.
Conclusions:
- CCl4 induces specific toxic effects on liver endoplasmic reticulum and polysomes, impairing protein synthesis.
- Spermine and arginine, particularly in combination, can effectively reverse CCl4-induced polysome disaggregation and stimulate protein production.
- This suggests a potential therapeutic strategy for CCl4-induced liver injury.