Premium
The assessment of chemically induced liver injury in rats
Author(s) -
Pritchard D. J.,
Wright M. G.,
Sulsh S.,
Butler W. H.
Publication year - 1987
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550070402
Subject(s) - coagulative necrosis , carbon tetrachloride , necrosis , centrilobular necrosis , lesion , pathology , ccl4 , medicine , liver injury , coagulation , chemistry , organic chemistry
The object of this investigation was to study the relationship between acute hepatic injury and blood coagulation. Most of the clotting factors are synthesised by the hepatocytes and therefore it would seem likely that hepatic injury would lead to an impairment of blood clotting. Dimethylnitrosamine (DMN) and carbon tetrachloride (CCI 4 ) were selected as model hepatotoxins to induce an acute hepatic lesion. Single doses of each compound were administered to male rats and groups of animals killed 3, 6, 16 and 24 h later in order to study the morphological development of the lesion and to relate this to changes in the haematological profiles. Both compounds produced a centrilobular necrosis, but with DMN there was a haemorrhagic component due to damage to endothelial cells, which contrasts with the classical coagulative necrosis produced by CCI 4 . After 6 h apoptosis was commonly seen in the centrilobular areas of the DMN treated rats. This process of cell death has not previously been demonstrated in chemically induced acute hepatic injury and was not seen in the CCI 4 treated rats. Significantly prolonged clotting times were seen in both DMN and CCI 4 treated rats and occurred in parallel with some of the early morphological changes but prior to the appearance of extensive haemorrhagic or coagulative necrosis. This preliminary data suggests that the measurement of blood coagulation times may provide a relatively specific and sensitive indicator of acute hepatic injury in rats.