Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model

Sugita,Satoshi; Inomata,Masafumi; Kono,Yohei; Shiroshita,Hidefumi; Etoh,Tsuyoshi; Shiraishi,Norio; Kitano,Seigo

doi:10.3892/ol.2013.1581

Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model

Authors:
- Satoshi Sugita
- Masafumi Inomata
- Yohei Kono
- Hidefumi Shiroshita
- Tsuyoshi Etoh
- Norio Shiraishi
- Seigo Kitano
View Affiliations

Affiliations: Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan
Published online on: September 12, 2013 https://doi.org/10.3892/ol.2013.1581
Pages: 1229-1233

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Radiation enterocolitis is a severe adverse event that occurs after radiotherapy for malignant abdominal tumors. In this study, the therapeutic effects of ETS‑GS, a novel vitamin E derivative with antioxidative and anti‑inflammatory abilities, were examined in a rat model of radiation enterocolitis. The radiation enterocolitis model was created by irradiation of male rats with a single dose of 10 Gy. ETS‑GS was administered subcutaneously (10 mg/kg/day) for five consecutive days from two days prior to irradiation. The animals were sacrificed three days after irradiation; following which, ileal tissue samples were analyzed for macroscopic and histological findings, presence of apoptosis, degree of oxidative stress and inflammation. In the irradiated group, severe erosion was observed in the small intestine in addition to necrosis of the mucosal layer, swelling and invasion of inflammatory cells of the submucosal layer, and shortening of the crypts. In irradiated rats that received ETS‑GS, mucosal injury in the small intestine was milder compared with that of irradiated rats that received no ETS‑GS. In addition, ETS‑GS decreased apoptosis in the small intestine and reduced the activity of myeloperoxidase and malondialdehyde, which are markers for inflammation and oxidative stress. ETS‑GS with antioxidant activity has a therapeutic effect on the symptoms of radiation enterocolitis in a rat model.

View Figures

View References

1	Kan S, Chun M, Jin YM, et al: A rat model for radiation-induced proctitis. J Korean Med Sci. 15:682–689. 2000. View Article : Google Scholar : PubMed/NCBI
2	Yeoh E and Horowitz M: Radiation enteritis. Br J Hosp Med. 39:498–504. 1988.
3	Ooi BS, Tjandra JJ and Green MD: Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer: an overview. Dis Colon Rectum. 42:403–418. 1999. View Article : Google Scholar : PubMed/NCBI
4	Kochhar R, Patel F, Dhar A, et al: Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci. 36:103–107. 1991.
5	Denton AS, Andreyev HJ, Forbes A and Maher EJ: Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer. 87:134–143. 2002. View Article : Google Scholar
6	Mennie AT, Dalley VM, Dinneen LC and Collier HO: Treatment of radiation-induced gastrointestinal distress with acetylsalicylate. Lancet. 2:942–943. 1975. View Article : Google Scholar : PubMed/NCBI
7	Stryker JA, Demers LM and Mortel R: Prophylactic ibuprofen administration during pelvic irradiation. Int J Radiat Oncol Biol Phys. 5:2049–2052. 1979. View Article : Google Scholar : PubMed/NCBI
8	Huang EY, Wang FS, Lin IH and Yang KD: Aminoguanidine alleviates radiation-induced small-bowel damage through its antioxidant effect. Int J Radiat Oncol Biol Phys. 74:237–244. 2009. View Article : Google Scholar : PubMed/NCBI
9	Abbasoğlu SD, Erbil Y, Eren T, Giriş M, et al: The effect of heme oxygenase-1 induction by octreotide on radiation enteritis. Peptides. 27:1570–1576. 2006.PubMed/NCBI
10	Giriş M, Erbil Y, Oztezcan S, et al: The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis. Am J Surg. 191:503–509. 2006.PubMed/NCBI
11	Kono Y, Inomata M, Hagiwara S, et al: A newly synthetic vitamin E derivative, E-Ant-S-GS, attenuates lung injury caused by cecal ligation and puncture-induced sepsis in rats. Surgery. 151:420–426. 2012. View Article : Google Scholar
12	Koga H, Hagiwara S, Inomata M, et al: Vitamin E derivative ETS-GS reduces liver ischemia-reperfusion injury in rats. J Surg Res. 175:118–122. 2012. View Article : Google Scholar : PubMed/NCBI
13	Hagiwara S, Koga H, Iwasaka H, et al: ETS-GS, a new anti-oxidative drug, protects against lipopolysaccharide-induced acute lung and liver injury. J Surg Res. 171:734–741. 2011. View Article : Google Scholar : PubMed/NCBI
14	Hagiwara S, Koga H, Iwasaka H, et al: ETS-GS, a new antioxidant, ameliorates renal ischemia-reperfusion injury in a rodent model. J Surg Res. 171:226–233. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hiratsuka T, Inomata M, Hagiwara S, et al: Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. Int J Colorectal Dis. 28:305–311. 2013. View Article : Google Scholar
16	Kikuchi A and Nishikawa T: Apoptotic and proliferating cells in cutaneous lymphoproliferative diseases. Arch Dermatol. 133:829–833. 1997. View Article : Google Scholar : PubMed/NCBI
17	El-Domyati M, Abo-Elenin M, El-Din WH, et al: Expression of apoptosis regulatory markers in the skin of advanced hepatitis-C virus liver patients. Indian J Dermatol. 57:187–193. 2012. View Article : Google Scholar : PubMed/NCBI
18	Kothakota S, Azuma T, Reinhard C, et al: Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science. 278:294–298. 1997. View Article : Google Scholar : PubMed/NCBI
19	Salvesen GS and Riedl SJ: Caspase mechanisms. Adv Exp Med Biol. 615:13–23. 2008. View Article : Google Scholar : PubMed/NCBI
20	Liu SH, Ma K, Xu XR and Xu B: A single dose of carbon monoxide intraperitoneal administration protects rat intestine from injury induced by lipopolysaccharide. Cell Stress Chaperones. 15:717–727. 2010. View Article : Google Scholar
21	Nielsen F, Mikkelsen BB, Nielsen JB, et al: Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem. 43:1209–1214. 1997.PubMed/NCBI
22	Mylonas PG, Matsouka PT, Papandoniou EV, et al: Growth hormone and insulin-like grouth factor I protect intestinal cells from radiation induced apoptosis. Mol Cell Endocrinol. 160:115–122. 2000. View Article : Google Scholar : PubMed/NCBI
23	Wang J, Zheng H, Sung CC, et al: The synthetic somatostatin analogue, octreotide, ameliorates acute and delayed intestinal radiation injury. It J Radiat Oncol Biol Phys. 45:1289–1296. 1999. View Article : Google Scholar
24	Emami B, Lyman J, Brown A, et al: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 21:109–122. 1991. View Article : Google Scholar : PubMed/NCBI
25	Nair CK, Parida DK and Nomura T: Radioprotectors in radiotherapy. J Radiat Res. 42:21–37. 2001. View Article : Google Scholar : PubMed/NCBI
26	Kilciksiz S, Demirel C, Erdal N, et al: The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model. Acta Med Okayama. 62:403–409. 2008.PubMed/NCBI
27	Perez CA: The Discipline of Radiation Oncology. Principles and Practice of Radiation Oncology. Perez CA, Brady LW, Halperin EC and Schmidt-Ullrich R: 4th edition. Lippincott Williams & Wilkins; Philadelphia: pp. 9–10. 2003
28	Hepgül G, Tanrikulu S, Unalp HR, et al: Preventive effect of pentoxifylline on acute radiation damage via antioxidant and anti-inflammatory pathways. Dig Dis Sci. 55:617–625. 2010.PubMed/NCBI
29	Mollà M, Gironella M, Salas A, et al: Protective effect of superoxide dismutase in radiation-induced intestinal inflammation. Int J Radiat Oncol Biol Phys. 61:1159–1166. 2005.PubMed/NCBI
30	Membrive Conejo I, Reig Castillejo A, Rodríguez de Dios N, et al: Prevention of acute radiation enteritis: efficacy and tolerance of glutamine. Clin Transl Oncol. 13:760–763. 2011.PubMed/NCBI
31	Takeda T, Kamiura S and Kimura T: Effectiveness of the herbal medicine daikenchuto for radiation-induced enteritis. J Altern Complement Med. 14:753–755. 2008. View Article : Google Scholar : PubMed/NCBI
32	Zimmerer T, Böcker U, Wenz F and Singer MV: Medical prevention and treatment of acute and chronic radiation induced enteritis - is there any proven therapy? a short review. Z Gastroenterol. 46:441–448. 2008. View Article : Google Scholar
33	Kono Y, Inomata M, Hagiwara S, et al: Antiproliferative effects of a new α-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro. Expert Opin Ther Targets. 16(Suppl 1): S103–S109. 2012.