Liver cirrhosis induced by carbon tetrachloride and the effect of superoxide dismutase and xanthine oxidase inhibitor treatment.
Repeated administration of carbon tetrachloride (CCl4) induces liver cirrhosis, possibly because it involves the production of free radicals. In order to evaluate the effect of free radical scavengers such as superoxide dismutase (SOD) and allopurinol in the pathogenesis of liver cirrhosis, rats were subjected to repeated CCl4 administration with and without scavengers. Four groups of animals were studied: CCl4 plus SOD (group 1), CCl4 plus allopurinol (group 2), CCl4 alone (group 3) and olive oil (group 4, normal controls). Analysis of plasma and tissue concentrations of trace elements was performed and histopathological patterns were studied in all groups after 7 weeks of repeated intraperitoneal administration of the solutions. Plasma levels of zinc and selenium were significantly lower in all experimental groups, with reciprocal elevation of manganese and copper. Copper and manganese content in the liver tissue was significantly higher in all three experimental groups. The zinc content was elevated in groups receiving CCl4 alone (group 3) or with allopurinol (group 2). The liver selenium, however, was significantly lower in these two groups. The copper:zinc ratio for plasma was 0.78 in the control group, 1.6 in the CCl4 group, 1.3 in the allopurinol group and 1.5 in the SOD group. For liver tissue, the ratio was 0.07 for controls, 0.17 for CCl4, 0.11 for allopurinol and 0.28 for the SOD group. The changes in trace element content correlated with the severity of cellular damage observed microscopically in the liver. The higher the copper:zinc ratio, the more advanced and extensive was the microscopic evidence of liver injury after CCl4 challenge.
Dashti
H M
HM
Department of Surgery, Faculty of Medicine, Kuwait University, Safat.
al-Sayer
H
H
Behbehani
A
A
Madda
J
J
Christenson
J T
JT
D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004195:Disease Models, Animal; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014131:Trace Elements / Q000032:analysis / Q000097:blood
D014131:Trace Elements; D000493:Allopurinol; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase