Copper overload in the developing guinea pig liver: a histological, histochemical and biochemical study.
The copper profile in Wilson's disease resembles that of human and guinea pig neonates. Microvesicular steatosis is characteristic of early histological damage in Wilson's disease. The aim of this study was to relate the histological, histochemical and ultrastructural changes seen in developing guinea pig liver to the developmental pattern of liver copper in these animals. Copper-stressed and control guinea pigs were studied. Liver biopsies were stained with haematoxylin and eosin, rhodanine (for copper), orcein (for copper-associated protein) and oil Red 0 (for fat). Selected specimens were examined by electron microscopy. Liver and serum copper levels and copper oxidase activity were also determined. Fetal liver copper increased during the last trimester of pregnancy, reaching five times the adult level in the perinatal period and falling rapidly in the 4 days after birth. Marked steatosis developed in both control and copper-stressed guinea pig liver. The fat score correlated strongly with liver copper concentration (r: 0.60; p less than 0.001). Orcein and rhodanine staining correlated with liver copper concentration (r: 0.52 and r: 0.40 respectively, p less than 0.01). Marked prenatal hepatic steatosis and its postnatal clearance correlates with changes in liver copper concentration. This experimental model provides an opportunity to study the pathogenesis of hepatic steatosis and the relationship between copper retention and steatosis.
Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
J
J
Chesta
S K
SK
Srai
A K
AK
Burroughs
P J
PJ
Scheuer
O
O
Epstein
D000818:Animals; D000831:Animals, Newborn; D003300:Copper / Q000032:analysis* / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D008099:Liver / Q000032:analysis* / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D010088:Oxidoreductases / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation
D003300:Copper; D010088:Oxidoreductases; C024748:copper oxidase