Cellular Hyperplasia in Rats Following Continuous Intravenous Infusion of Recombinant Human Epidermal Growth Factor

Abstract

In this study, we determined in vivo morphologic effects of continuous intravenous infusion of recombinant human epidermal growth factor (EGF) in adult Wistar rats. The EGF used consisted of the amino acid residues 1-48 of the human 53-amino-acid EGF molecule, purified from transfected Escherichia coli. Doses of 25, 100, or 250 micrograms/kg body weight were administered using Harvard digital syringe infusion pumps for 4 weeks. At necropsy, the submandibular salivary glands, Harderian glands, liver, kidneys (females only), and ovaries were enlarged and urinary bladders were thickened in 100- and 250-micrograms/kg rats. Numerous tissues of the 100- and 250-micrograms/kg rats contained hyperplastic epithelial cells, and selected organs also had mesenchymal cell proliferation. Epithelial proliferation was most pronounced in the trachea, nasal cavity, nasolacrimal duct, tongue, stomach, small intestine, large intestine, urinary tract, salivary gland ducts, and Harderian gland. Periportal hepatocytes were hypertrophic, correlating with increased liver weight. In addition, mesenchymal cell proliferation was evident in the gastric mucosa lamina propria and in heart valves in 100- and 250-micrograms/kg rats. Increased ovarian weight correlated with increased number and size of corpora lutea and an increased incidence of luteal cysts. Continuous systemic exposure of adult Wistar rats to high doses of EGF resulted in generalized epithelial hyperplasia and tissue-selective mesenchymal proliferation.

The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

“…The observed effect of IGF-I infusion on kidney weight is consistent with earlier findings (Gruaz et al 1997, van Neck et al 1997, as is the ineffectiveness of EGF on kidney growth (Frystyk et al 1996). This is in contrast to the findings of Breider et al (1996) who infused male and female animals with (n=8) and expressed relative to placebo control. *P=0·05, **P=0·03, statistical significance level between the indicated group and the placebo control.…”

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment

“…Because rat EGF was not commercially available, hEGF was used for this experiment. Literature shows sufficient evidence that hEGF works in rats in the concentration used in this experiment (4,17,45).…”

Digestive System

“…This was characterized by a uniform increase in the thickness of the squamous epithelium in both species. 26,27 At high doses, the squamous epithelium of the tongue of the primates was twice the thickness of control mucosa and was associated with elongation of rete pegs. Conversely, interference of growth factor activity by inhibition of tyrosine kinases associated with the epidermal growth factor receptor appears to be associated with mouth inflammation and ulceration in some patients although this is found less commonly than skin changes.…”