To examine the protective effects of hepatocyte growth-promoting factor (pHGF) against carbon tetrachloride (CCl
4) -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 CCl
4(2m
l/kg BW) in two groups of animals, of which one received pHGF (300μg/kg BW) via the tail vein after 4 hrs. In the group treated with CCl
4 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 CCl
4. 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 CCl
4 followed by pHGF, serum GOT and GPT levels were significantly lower than in the CCl
4-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 CCl
4-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 CCl
4-induced hepatic injury.
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