Absorption of epidermal growth factor occurs through the gastrointestinal tract and oral cavity in adult rats

Abstract

Introduction of radiolabeled epidermal growth factor (125I-EGF) by gavage or sublingual confinement resulted in a time-dependent uptake and systemic organ dissemination in the adult rat. Intact EGF was recovered primarily from the tongue, parotid, and sublingual/submandibular glands after administration by sublingual lozenge, whereas gastrointestinal administration resulted in 125I-EGF recovery primarily from plasma, stomach, and lung. Recovered radiolabeled EGF retained the ability to bind to the EGF receptor. Sialoadenectomy caused an increase in 125I-EGF in most tissues by both routes of administration. Thus, in the adult rat, at least two pathways exist for the uptake and distribution for salivary gland-derived EGF present in saliva. With further analyses, sublingual absorbance of EGF may therefore provide a potential delivery route for therapeutic use of growth factor, which avoids the hepatic destruction of EGF after oral administration.

Epidermal Growth Factor Protects against Pancreatic Damage in Cerulein-Induced Pancreatitis

“…It was reported that absorption of a substantial amount of EGF occurs through the mucosa of the oral cavity in adult rats [31]and the excision of salivary glands aggravates experimental gastric ulcers [15, 17], but in our present study we could not find any strong evidence for aggravation of pancreatitis after salivectomy. The data obtained are not consistent.…”

Heparin-Binding Epidermal Growth Factor-Like Growth Factor Protects Rat Intestine from Ischemia/Reperfusion Injury

“…While it is possible that HB-EGF exerted its effect in our model via absorption into the bloodstream, it is also possible that it acted locally via direct contact with enterocyte EGFR. The gastrointestinal absorption of HB-EGF has never been reported; however, absorption of EGF was demonstrated after oral administration in suckling rats [44] and gastric or oral administration in adult rats [45]. Future experiments are needed to address the intestinal absorption of HB-EGF.…”

Exposure assessment of epidermal growth factor to various tissues in mice after intravenous and subcutaneous administration

“…Tissue distribution of 125 I–EGF was previously examined in mice, pigs and rats [33,41,42]. After oral administration of 125 I‐EGF in rats, the radioactivity in tissues reached a maximum by 30 min and declined thereafter [35]. At 2.5 min after intravenous injection of 125 I‐EGF, the highest fraction of injected radioactivity determined was found in liver (52%) followed by kidney (14%), small intestine (11%), skin (7%), spleen (0.8%) and lung (0.6%) [41].…”

“…Various studies have been conducted to examine the plasma pharmacokinetics of EGF after topical,[31] subcutaneous,[32] oral,[33,34] sublingual,[35] rectal[36] and intravenous[36–40] administration in rats, mice and dogs. Tissue distribution studies have also been performed in rats, pigs and mice by determining total radioactivity after intravenous, oral and sublingual administration of 125 I‐EGF [33,41,42].…”