Koji Fukuda1, Yoshihiko Uehara2, Eiko Nakata3, Masahiro Inoue1, Kazuhiro Shimazu1, Taichi Yoshida1, Hiroaki Kanda4, Hiroshi Nanjo5, Yoshio Hosoi2, Hiroyuki Yamakoshi6, Yoshiharu Iwabuchi6, Hiroyuki Shibata1. 1. a Department of Clinical Oncology , Graduate School of Medicine, Akita University , Akita , Japan ; 2. b Laboratory for Radiation Biology , Tohoku University , Sendai , Japan ; 3. c Department of Radiation Oncology , Graduate School of Medicine, Tohoku University , Sendai , Japan ; 4. d Division of Pathology , Cancer Institute, Japanese Foundation for Cancer Research , Tokyo , Japan ; 5. e Department of Clinical Pathology , Graduate School of Medicine, Akita University , Akita , Japan ; 6. f Department of Organic Chemistry , Graduate School of Pharmaceutical, Tohoku University , Sendai , Japan.
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.
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.