Early recombinant human epidermal growth factor treatment recovers the irradiation-induced decrease of Na+ absorption prior to the definite histological mucositis

• Published in: Biomedicine & pharmacotherapy Vol. 64; no. 9; pp. 594 - 599
• Main Authors: Kim, Jin Kyoung, Kim, Chung Su, Ahn, Hyun Joo, Bang, Si Ra, Kim, Sung Joon, Yoo, Hae Young, Jeong, Han-Sin
• Format: Journal Article
• Language: English
• Published: Paris Elsevier SAS 01.11.2010; Elsevier
• Subjects: Absorption - drug effects; Animals; Biological and medical sciences; Body Weight - drug effects; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Epidermal Growth Factor - therapeutic use; Epithelium; Epithelium - drug effects; Epithelium - metabolism; Epithelium - pathology; Female; Humans; Internal Medicine; Ion transport; Ion Transport - drug effects; Medical Education; Medical sciences; Mice; Mice, Inbred C3H; Mucositis - drug therapy; Mucositis - metabolism; Mucositis - pathology; Pharmacology. Drug treatments; Radiation; Radiation Injuries, Experimental - drug therapy; Radiation-Protective Agents - pharmacology; Radiation-Protective Agents - therapeutic use; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Short circuit current; Sodium - metabolism; Trachea - drug effects; Trachea - metabolism; Trachea - pathology; Ion transport; Epidermal growth factor; Epithelium; Short circuit current; Radiation; Human; Mucositis; Circuit; Histology; Absorption; Treatment; Sodium; Irradiation; Early; Mucosa disease; Recombinant protein; Pharmacokinetics
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2010.06.005

Abstract Recombinant human epidermal growth factor (rhEGF) has potential benefit for the mucositis induced by radiation therapy as a therapeutic setting. In this study, we aimed to investigate the effects of rhEGF treatment on the radiation-induced changes in epithelial transport function, before the occurrence of the definitive histological mucosal changes. C3H/He mice received 0, 4, or 8 Gy irradiation and/or EGF treatment (rhEGF 0, 1 and 5 mg/kg, i.p., 5 days). At day 7, we recorded short circuit current ( Isc ) of the upper tracheal epithelium using the flow-type Ussing chamber method, with histological analysis. As a result, there was no evident pathological change in the epithelium from the irradiated and/or rhEGF treated mice at day 7. The initial level of Isc and amiloride-sensitive Isc (Δ Isc,Amil ) were decreased after 8 Gy irradiation, reflecting suppression of basal Na+ absorption. The decreased Δ Isc,Amil was recovered by rhEGF treatment. In conclusion, epithelial Na+ channel-dependent basal Na+ absorption was primarily affected by irradiation, before the pathological changes. The recovery of basal Na+ absorption (Δ Isc,Amil ) suggested a potentially beneficial effect of early rhEGF treatment for irradiation-induced suppression of the upper aerodigestive epithelial functions.