A diarylpentanoid curcumin analog exhibits improved radioprotective potential in the intestinal mucosa

Int J Radiat Biol. 2016 Jul;92(7):388-94. doi: 10.3109/09553002.2016.1164910. Epub 2016 Apr 4.

Abstract

Purpose: To best enhance the effects of radiotherapy, it is important to minimize adverse events, including free radical-induced intestinal cell damage. Given the threat of nuclear power plant accidents or nuclear terrorism, there is an urgent need for radioprotectants to counteract the radiation-induced toxicity and/or injuries. Curcumin exhibits protective effects against gamma irradiation; however, its in vivo efficacy is decreased due to the low bioavailability. We examined the radioprotective effect of a newly synthesized curcumin analog, GO-Y031, on 11-Gy X-ray-induced intestinal mucosal damage in mice.

Materials and methods: The radioprotection experiments were conducted by using C57BL/6J or Jcl:ICR mice. Molecules related to radiation damage, including p53, Bax, Bcl-2, cleaved caspase-3, and reactive carbonyl species (RCS), were investigated immunohistochemically.

Results: GO-Y031 protected against crypt hypoplasia relative to a mock treatment at 0.5% (weight/weight); the number of crypts were 11.00 ± 2.00/circumference (mm) in treated versus 6.86 ± 0.99/mm in mock-treated C57BL/6 mice (p = 0.0079). GO-Y031 also reduced the levels of RCS, p53, and cleaved caspase-3 accumulation in the irradiated intestinal cells.

Conclusions: GO-Y031 suppresses the accumulation of RCS and apoptosis-related molecules in irradiated cells. This compound may be a good primary radioprotective compound.

Keywords: Curcumin; intestinal damage; radioprotection.

MeSH terms

  • Animals
  • Benzene Derivatives
  • Curcumin / administration & dosage
  • Curcumin / analogs & derivatives*
  • Dose-Response Relationship, Radiation
  • Ketones
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mouth Mucosa / pathology
  • Mouth Mucosa / radiation effects*
  • Radiation Dosage
  • Radiation Injuries / pathology*
  • Radiation Injuries / prevention & control*
  • Radiation Tolerance / physiology
  • Radiation-Protective Agents / administration & dosage
  • Stomatitis / pathology*
  • Stomatitis / prevention & control*

Substances

  • 1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one
  • Benzene Derivatives
  • Ketones
  • Radiation-Protective Agents
  • Curcumin