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

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
• radioprotection
• intestinal damage

Acknowledgements

This study was partially supported by the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research [C] 22501041 to Y.U., Y.I., and H.S.) and Nippon Carbide Industries Co., Inc (Tokyo, Japan). The authors also would like to thank Enago (www.enago.jp) for the English language review.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.