Hepatic fibrogenesis using chronic arsenic ingestion: studies in a murine model.
Chronic oral arsenic (As) ingestion has been alleged to cause hepatic fibrosis, non-cirrhotic portal fibrosis and cirrhosis of the liver. The present study was aimed to investigate if hepatic fibrogenesis and non-cirrhotic portal fibrosis (NCPF) is caused by arsenic. A significant increase in the hepatic protein and collagen was seen compared with controls; hepatic 4-hydroxyproline levels, indicative of fibrogenesis, were increased 4-14 folds with different dosages of arsenic compared to the controls. Hepatocellular necrosis and inflammation were negligible to mild in all the groups. None of the animals developed significant splenomegaly or features of non-cirrhotic portal hypertension. The results suggest that (i) prolonged oral arsenic ingestion in mice leads to significant hepatic fibrogenesis and collagen synthesis with minimal hepato-cellular injury; (ii) arsenic ingestion alone is unlikely to cause non-cirrhotic portal fibrosis or cirrhosis of liver. This murine model of arsenic feeding could be used for the evaluation of new antifibrotic agents for the liver.
Sarin
S K
SK
Department of Gastroenterology and Pathology, G B Pant Hospital, New Delhi, India. ssarin@giasdla.vsnl.net.in
Sharma
G
G
Banerjee
S
S
Kathayat
R
R
Malhotra
V
V
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D003094:Collagen; D001151:Arsenic; D006909:Hydroxyproline