Oxidative stress in the development of liver cirrhosis: a comparison of two different experimental models.
OBJECTIVE
Oxidative stress has been implicated in liver cirrhosis. Carbon tetrachloride and thioacetamide are the most widely used models to develop cirrhosis in rats and the present study compares oxidative stress in the liver induced by these compounds at different stages of cirrhosis development.


METHODS
Twice-weekly intragastric or intraperitoneal administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months. Histology, serum markers and hepatic hydroxy proline content confirmed the cirrhosis.


RESULTS
An increase in oxidative stress parameters was seen in mitochondria, peroxisomes and microsomes from the liver after carbon tetrachloride or thioacetamide treatment. Oxidative stress was more severe in carbon tetrachloride treated animals than thioacetamide. Mild oxidative stress was evident at 1 and 2 months of treatment and a significant increase was seen by 3 months of treatment with either compound. By this time, frank liver cirrhosis was also observed.


CONCLUSIONS
These results suggest that evidence of oxygen free radicals is also found early in the development of fibrosis and cirrhosis in both models.
Natarajan
Sathish Kumar
SK
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India. wellcome@cmcvellore.ac.in
Thomas
Simmy
S
Ramamoorthy
Prabhu
P
Basivireddy
Jayasree
J
Pulimood
Anna B
AB
Ramachandran
Anup
A
Balasubramanian
Kunissery A
KA
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D008933:Mitochondrial Swelling; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity
D015415:Biomarkers; D013853:Thioacetamide; D002251:Carbon Tetrachloride