Experimental study on rat hepatic injury by copper--effect of copper overload on the cholestatic liver induced by bile duct ligation
Shibuya, H.
Hokkaido Journal of Medical Science 62(3): 434-441
1987
ISSN/ISBN: 0367-6102 PMID: 3610036 Document Number: 4136
In the cases of protracted obstructive jaundice, it is reported that there was a positive correlation between the hepatic copper concentration and the severity of destruction of the bile ducts. The author produced the model of obstructive jaundice in rats by common bile duct ligation and investigated whether additional copper overload can cause injury on the liver. The simple ligating procedure induced a significantly increased level of the copper concentration (p less than 0.001). The copper concentration of the group with the additional copper overload showed about an eighteen-fold increase in comparison with the group of the only ligation (p less than 0.005). Histologically, the group with the overload alone exhibited no significant finding. The groups with the ligation showed bile duct proliferation with subsequent fibrosis around portal areas (pericholangiolar fibrosis); however, the fibrosis in the group with an additional overload was more prominent than that without an additional overload. By the orcein stain, the positive granules in the group with the ligation alone were preferentially present in the liver cells around the proliferated bile ducts. The group with the additional overload exhibited diffuse and more pronounced staining. Ultrastructurally, the liver cells in the group with the additional overload contained lysosomes with electron-dense material, some of which showed a feature consistent with focal interruption of their membranes. By X-ray microanalysis, these lysosomes were revealed to include copper as well as sulfur. The sulfur was considered to represent copper-binding protein.
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