EPIDERMAL GROWTH-FACTOR PROTECTS AGAINST CARBON TETRACHLORIDE-INDUCEDHEPATIC-INJURY

1, Epidermal growth factor (EGF) is known to protect the gastrointesti nal tract against various noxious agents, Its potential value in preve nting/treating hepatic injury is, however, largely unexplored, We ther efore examined whether EGF could influence CCl4-induced hepatic injury , 2, Female Sprague-Dawley rats (8 per group) received saline or recom binant EGF (500 or 750 mu g/kg, intraperitoneal) 30 min before CCl4 (2 0% v/v, in olive oil, intraperitoneal), Eighteen hours later, animals were killed, serum was collected for assay of biochemical markers of h epatic injury and livers were removed for histological analyses, 3, Ad ministration of CCl4 resulted in severe hepatic necrosis and caused a 10-fold rise in plasma alanine aminotransferase levels compared with l evels seen in control animals (218 +/- 15 compared with 23+/-9 mu mol/ l in controls, mean+/-SEM, P<0,01), Serum malondialdehyde levels, used as a marker of lipid peroxidation, showed a 2-fold rise in response t o CCl4 treatment (median 4.0, quartile range 3.3-5.8 units/l compared with median 2.3, quartile range 2.1-2.5 units/l in controls, P < 0.05) , Administration of EGF at 500 mu g/kg, before the CCl4 did not protec t against injury, as assessed by histology or rise in plasma alanine a minotransferase levels, In contrast, animals given EGF at 750 mu g/kg, before the CCl4, had only minimal changes in histology; ,vith only a minor rise in alanine aminotransferase levels (37+/-4 compared with 23 +/-9 mu mol/l in animals not given CCl4) and had no significant rise i n malondialdehyde levels, 4, EGF protects against CCl4-induced hepatic injury and may provide a novel approach to the treatment of liver dam age.