Does oxidative protein damage play a role in the pathogenesis of carbon tetrachloride-induced liver injury in the rat?
Free radicals have been implicated in the pathogenesis of alcohol-induced liver injury in humans and carbon tetrachloride (CCl4)-induced liver injury in rats. The most extensively studied aspect of free radical induced liver injury is lipid peroxidation. Recently it has been found that free radicals can cause oxidative damage to cellular proteins and alter cellular function. One such susceptible protein is the enzyme glutamine synthase (GS). The chemical effects of CCl4 on cell proteins and their biological consequences are not known. Hence, in our study, the effect of CCl4 on liver protein oxidation and GS activity were investigated and compared with lipid peroxidation. A significant increase in liver protein carbonyl content (2-3 fold) and a significant decrease in hepatic GS activity (44-57%) were observed. Damage to proteins was rapid in onset and increased with time. Acute exposure of rats to CCl4 resulted in an increase in hepatic protein carbonyl content and a decrease in hepatic GS within 1 h. In cirrhosis of the liver induced by CCl4, the decrease in hepatic GS activity was accompanied by a significant increase in plasma ammonia levels. We conclude that protein oxidation may play a role in the pathogenesis of CCl4 induced liver injury and that the accumulation of oxidised proteins may be an early indication of CCl4 induced liver damage.
Sundari
P N
PN
Department of Biochemistry, Christian Medical College & Hospital, Vellore, Tamilnadu, India.
Wilfred
G
G
Ramakrishna
B
B
D000208:Acute Disease; D000641:Ammonia / Q000097:blood; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D002908:Chronic Disease; D005609:Free Radicals; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology; D008297:Male; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D008054:Lipid Peroxides; D011506:Proteins; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase