title: Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice.
abstract: Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies to control the regeneration of damaged mucosa.
authors.affiliation: Research Program for Radiation Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishihara
authors.forename: Izumi
authors.initials: I
authors.lastname: Tanaka
authors.forename: Haruko
authors.initials: H
authors.lastname: Yakumaru
authors.forename: Mika
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yokochi
authors.forename: Makoto
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D006062:Gonadotropins / Q000008:administration & dosage*; D006632:Histamine / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000254:growth & development / Q000293:injuries*; D007421:Intestine, Small / Q000187:drug effects / Q000254:growth & development / Q000293:injuries*; D008297:Male; D008713:Methimazole; D051379:Mice; D008809:Mice, Inbred C3H; D015282:Octreotide / Q000008:administration & dosage*; D011832:Radiation Injuries / Q000188:drug therapy* / Q000209:etiology; D012038:Regeneration / Q000187:drug effects*; D015996:Survival Rate; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D006062:Gonadotropins; D008713:Methimazole; D006632:Histamine; D015282:Octreotide
keywords: anabolic steroid; glucagon; histamine; radiation accident; thyroid hormone