title: Early recombinant human epidermal growth factor treatment recovers the irradiation-induced decrease of Na+ absorption prior to the definite histological mucositis.
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 5mg/kg, i.p., 5 days). At day 7, we recorded short circuit current (I(sc)) 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 I(sc) and amiloride-sensitive I(sc) (ΔI(sc,Amil)) were decreased after 8 Gy irradiation, reflecting suppression of basal Na+ absorption. The decreased ΔI(sc,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 (ΔI(sc,Amil)) suggested a potentially beneficial effect of early rhEGF treatment for irradiation-induced suppression of the upper aerodigestive epithelial functions.
authors.affiliation: Department of Anesthesiology-Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jin Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Chung Su
authors.initials: CS
authors.lastname: Kim
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Si Ra
authors.initials: SR
authors.lastname: Bang
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Yoo
authors.forename: Han-Sin
authors.initials: HS
authors.lastname: Jeong
mesh_terms: D000042:Absorption / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D052016:Mucositis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D012964:Sodium