Epidermal growth factor protects against carbon tetrachloride-induced hepatic injury

1. Epidermal growth factor (EGF) is known to protect the gastrointestinal tract against various noxious agents. Its potential value in preventing/treating hepatic injury is, however, largely unexplored. We therefore examined whether EGF could influence CCl 4 -induced hepatic injury. 2. Female Sprague-Dawley rats (8 per group) received saline or recombinant EGF (500 or 750 μg/kg, intraperitoneal) 30 min before CCl 4 (20% v/v, in olive oil, intraperitoneal). Eighteen hours later, animals were killed, serum was collected for assay of biochemical markers of hepatic injury and livers were removed for histological analyses. 3. Administration of CCl 4 resulted in severe hepatic necrosis and caused a 10-fold rise in plasma alanine aminotransferase levels compared with levels seen in control animals (218 ± 15 compared with 23 ± 9 μmol/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 to CCl 4 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 μg/kg, before the CCl 4 , did not protect against injury, as assessed by histology or rise in plasma alanine aminotransferase levels. In contrast, animals given EGF at 750 μg/kg, before the CCl 4 , had only minimal changes in histology, with only a minor rise in alanine aminotransferase levels (37 ± 4 compared with 23 ± 9 μmol/l in animals not given CCl 4 ) and had no significant rise in malondialdehyde levels. 4. EGF protects against CCl 4 -induced hepatic injury and may provide a novel approach to the treatment of liver damage.