Sequential Morphological Changes of Copper Overloaded-Rat Liver: Ultrastructural Study

Han, Nam Ik; Choi, Sang Duk; Chung, Kyu Won; Nam, Soon Woo; Han, Joon Yeol; Choi, Sang Wook; Lee, Young Sok; Sun, Hee Sik

Abstract

BACKGROUND/AIMS: This study was designed to clarify the sequential morphologic changes of copper overloaded-rat liver. METHODS: The Sprague-Dawley rats were divided into three groups according to copper and penicillamine administration: Group I. normal control injected with lipiodol; Group II, treated with copper only; Group III, treated with copper plus D-penicillamine. Liver tissues were stained with hematoxylin-eosin and rubeanic acid. In order to elucidate the ultrastructural changes of the liver, transmission electron microscopic examination was also performed. RESULTS: Electron microscopic findings in copper-treated group were characterized by a number of copper-containing lysosomes at pericanalicular ectoplasm, normal sized and bizarre mitochondria with small vacuoles (at 2 weeks), dilated bile canaliculi with decreased microvilli (at 3 weeks), disruption of sinusoidal border (at 4 weeks), microsteatosis (at 5 weeks), a Councilman body-like inclusion in sinusoid and round hepatocytes undergone coagulation necrosis in sinusoid (at 7 weeks), increased collagen bundles in Disse space and loss of microvilli (at 12 weeks). There were increased copper containing granules in hepatocytes of copper plus D-penicillamine treated group, but normal ultrastructural findings were observed. CONCLUSIONS: These findings indicate that hepatic injury induced by copper overload is caused by deranged copper metabolism in the lysosome of the hepatocytes and administration of D-penicillamine in copper stressed rats seems to be effective for the restoration of hepatocyte function and morphologic changes.