Recombinant human epidermal growth factor accelerates recovery of mouse small intestinal mucosa after radiation damage

Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1230-5. doi: 10.1016/j.ijrobp.2008.03.041.

Abstract

Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation.

Methods and materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate.

Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups.

Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Epidermal Growth Factor / administration & dosage*
  • Epidermal Growth Factor / genetics
  • Intestinal Diseases / drug therapy*
  • Intestinal Diseases / etiology
  • Intestinal Diseases / physiopathology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / physiopathology*
  • Intestine, Small
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Radiation Injuries / drug therapy*
  • Radiation Injuries / etiology
  • Radiation Injuries / physiopathology*
  • Radiation-Protective Agents / administration & dosage
  • Recombinant Proteins / administration & dosage
  • Recovery of Function / drug effects*
  • Treatment Outcome

Substances

  • Radiation-Protective Agents
  • Recombinant Proteins
  • Epidermal Growth Factor