Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen

Dimethylnitrosamine (DMN) is a potent hepatotoxin that can cause fibrosis o f the liver. It's ability to provide a suitable rapid experimental murine m odel for early human cirrhosis was examined. The drug was administered to a dult male albino rats in order to document sequential pathological and bioc hemical alterations. Injury was produced by intraperitoneal injections of D MN on three consecutive days of each week over a 3-week period. A rapid inc rease in collagen content was documented, with linear increases occurring f rom days 7 to 21. Livers were examined for histopathological changes on day s 7, 14 and 21 following the beginning of exposure. severe centrilobular co ngestion and haemorrhagic necrosis could be observed on day 7. Centrilobula r necrosis and intense neutrophilic infiltration were observed on day 14. B y day 21, collagen fiber deposition could be observed, together with severe centrilobular necrosis, with focal Fatty changes, bile duct proliferation, bridging necrosis and fibrosis surrounding the central veins. A decrease i n total protein and increase in DNA were also documented. DMN-induced liver injury in rats appears to be a potential animal model For early human cirr hosis and the rapid deposition of collagen, and mag serve as a convenient p rocedure for screening antifibrotic agents. (C) 2001 Elsevier science Irela nd Ltd. All rights reserved.