George J, Rao K R, Stern R, Chandrakasan G
Department of Biochemistry, Central Leather Research Institute, Adyar, Chennai600 020, India.
Toxicology. 2001 Jan 2;156(2-3):129-38. doi: 10.1016/s0300-483x(00)00352-8.
Dimethylnitrosamine (DMN) is a potent hepatotoxin that can cause fibrosis of the liver. It's ability to provide a suitable rapid experimental murine model for early human cirrhosis was examined. The drug was administered to adult male albino rats in order to document sequential pathological and biochemical alterations. Injury was produced by intraperitoneal injections of DMN on three consecutive days of each week over a 3-week period. A rapid increase in collagen content was documented, with linear increases occurring from days 7 to 21. Livers were examined for histopathological changes on days 7, 14 and 21 following the beginning of exposure. Severe centrilobular congestion and haemorrhagic necrosis could be observed on day 7. Centrilobular necrosis and intense neutrophilic infiltration were observed on day 14. By 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 in 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 cirrhosis and the rapid deposition of collagen, and may serve as a convenient procedure for screening antifibrotic agents.
