Cirrhosis of the liver induced by cupric nitrilotriacetate in Wistar rats. An experimental model of copper toxicosis.
Rats intraperitoneally injected with a daily dose of cupric nitrilotriacetate (Cu-NTA), which contained 4 to 7 mg of copper/kg body weight, showed submassive liver necrosis, hemolytic anemia, and acute renal tubular necrosis at the beginning of the experiment and intermittently after 4 weeks of injections. All rats that survived over 8 weeks exhibited liver fibrosis with portal-portal, portal-central, and central-central bridging. In all rats that survived over 16 weeks, micronodular cirrhosis of the liver or extensive liver fibrosis was observed. The copper content of the cirrhotic/fibrotic liver was above 250 micrograms/g dry weight. Electron-microscopic x-ray analysis at day 93 revealed that copper stored in secondary lysosomes was always accompanied by a proportional amount of sulfur (correlation coefficient, 0.98; P less than 0.005). An experimental model of copper toxicosis in terms of copper-induced cirrhosis of the liver was established with exogenous copper chelated by nitrilotriacetate.
Toyokuni
S
S
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Okada
S
S
Hamazaki
S
S
Fujioka
M
M
Li
J L
JL
Midorikawa
O
O
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D003300:Copper / Q000032:analysis / Q000633:toxicity*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007501:Iron / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000000981:diagnostic imaging / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000633:toxicity*; D009942:Organometallic Compounds / Q000032:analysis / Q000633:toxicity*; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D009942:Organometallic Compounds; D003300:Copper; C060581:cupric nitrilotriacetate; D007501:Iron; D009571:Nitrilotriacetic Acid