[The protective effect of hepatocyte growth-promoting factor (pHGF) against carbon tetrachloride-induced acute liver injury in rats. II. Protective effects on cell membrane injury].
To examine the protective effects of hepatocyte growth-promoting factor (pHGF) against carbon tetrachloride (CCl4) -induced acute liver injury in rats, the pathological changes were observed by light and electron microcopy, and the serum GOT and GPT levels were measured. Acute liver injury was produced by the injection of CCl4 (2ml/kg BW) in two groups of animals, of which one received pHGF (300 microg/kg BW) via the tail vein after 4 hrs. In the group treated with CCl4 alone, serum GOT and GPT were significantly elevated (1280+/-228 and 187+/-73 IU/l, respectively) 6 hrs after injection, indicating the induction of liver injury by CCl4. They reached a peak (3836+/-654 and 1022+/-230 IU/l, respectively) at 48 hrs and declined thereafter, but did not completely recover after 72 hrs. PAS-negative cells were observed around the central veins after 6 hrs and most of the hepatocytes were PAS-negative at 12 hrs. PAS-positive cells began to appear and increased in number after 24 hrs. There were scarcely any PAS-negative cells remaining in the lobules after 72 hrs. In the group treated with CCl4 followed by pHGF, serum GOT and GPT levels were significantly lower than in the CCl4-treated group, and abundant PAS-positive hepatocytes were observed. Also, all hepatocytes were PAS-positive (as in normal liver) after 72 hrs. Administration of pHGF resulted in a decrease in the ultrastructural changes in rats with CCl4-induced liver injury such as vacuolation, cisternae formation and dilatation of the rough endoplasmic reticulum. These results suggest that pHGF acts to stabilize cell membranes, thereby providing protection against CCl4-induced hepatic injury.
Dai
W
W
Department of Pathology and Central Institute for Electron Microscopic Researches, Nippon Medical School, Tokyo, Japan.
Sato
S
S
Asano
G
G
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D004721:Endoplasmic Reticulum / Q000648:ultrastructure*; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D008099:Liver / Q000648:ultrastructure; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar
D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase