Milk-borne epidermal growth factor modulates bilirubin levels in neonatal rats

SummaryObjectivesBreast milk jaundice (BMJ) is commonly of undetermined etiology. Recently, it has been shown that the degree of BMJ was associated with the increased levels of milk-borne EGF (Epidermal Growth Factor). The aim of the present study was to test the effects of enteral administration of EGF on the development of hyperbilirubinemia in neonatal rats.MethodsPups were divided into three groups: Group 1; artificially fed with formula, Group 2; artificially fed with formula supplemented with 500 ng/ml rat EGF, Group 3; fed by their mothers. Hyperbilirubinemia was induced by an intraperitoneal injection of unconjugated bilirubin suspension once daily for 5 consecutive days. Bilirubin levels, length of ideal villi, and EGF-R expression in the intestine was determined at postnatal day 6.ResultsIn the groups of 2 and 3, serum bilirubin levels were significantly higher when compared to animals in the group 1. There was no significant difference in terms of serum bilirubin levels between the Group 2 and Group 3. Length of ileal villi was significantly longer in the Group 2 and Group 3 than the Group 1 animals. The pattern of EGF-R expression in the Group 2 was similar to that seen in Group 3 animals. In contrast, animals given formula without EGF had markedly decreased expression of the EGF-R.ConclusionResults suggest that EGF supplementation in newborn rats leads to a significant increase in intestinal mucosal proliferation and a significant decrease in bilirubin elimination. These data suggest that EGF possibly increases intestinal bilirubin absorption and may have a role in development of breast milk jaundice. Further studies are needed to confirm this hypothesis.