Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application.
Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.
Federal Environmental Agency, Institute for Water-, Soil- and Air-Hygiene, Berlin, Germany.
F
F
Schiller
U
U
Lippold
R
R
Heinze
A
A
Hoffmann
W
W
Seffner
D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001646:Bile / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D006168:Guinea Pigs; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D015996:Survival Rate
D003300:Copper; D016604:Aflatoxin B1